#215 - The gut-brain connection | Michael Gershon, M.D.
Dr. Mike Gershon, Professor of Pathology and Cell Biology at Columbia University, provides a foundational understanding of the gut's unique anatomy, its intrinsic nervous system, and bidirectional communication with the brain. He discusses the gut microbiome, the impact of diet, antibiotics, and the limitations of commercial gut tests.
Deep Dive Analysis
17 Topic Outline
Introduction to the GI System and Its Embryology
Unique Challenges and Anatomy of the GI Tract
Vascular Supply and Portal System of the Gut
The Enteric Nervous System: The Gut's 'Second Brain'
Gut-Brain Communication and CNS Influence
Pain Sensation and Distinct Behaviors of the Gut
Regulation of Appetite and Satiety Signals
Impact of Gastric Bypass Surgery on Satiety
Varicella Zoster Virus (Shingles) Infection in the Gut
Autism Spectrum Disorder and Gastrointestinal Issues
The Role of Serotonin in the Gut and SSRI Effects
Understanding 'Leaky Gut' and Its Causes
The Gut Microbiome: Composition and Function
Fecal Transplants: Use Cases and Limitations
Utility of Gut Microbiome Diagnostic Tests
Nutritional Approaches for Optimal Gut Flora
Prebiotics, Probiotics, and Post-Antibiotic Recovery
6 Key Concepts
GI Tract as External Space
The gastrointestinal tract, from mouth to anus, is fundamentally an internalized external space. Its interior is considered outside the body, posing a unique challenge for nutrient absorption while maintaining a protective barrier against external organisms and toxins.
Enteric Nervous System (ENS)
Often called the 'second brain,' the ENS is the gut's intrinsic nervous system, capable of functioning and controlling reflexes and behavior independently of the brain or spinal cord. It consists of two main plexuses: the submucosal (Meissner's) plexus and the myenteric (Auerbach's) plexus, which communicate with each other and the CNS.
Tight Junctions
These are protein structures in the membranes of adjacent epithelial cells that line cavities, like the gut. They essentially 'plug' the space between cells, preventing material from passing through the intercellular channel and maintaining the integrity of the gut barrier.
Serotonin in the Gut
About 95% of the body's serotonin is produced in the gut by enterochromaffin cells and serotonin-containing nerve cells. In the gut, serotonin acts as a neurotransmitter, an endocrine substance, a growth factor for nerve cells, and is involved in pain sensation, nausea, inflammation, and peristaltic reflexes.
Leaky Gut
This term refers to a condition where the tight junctions between epithelial cells in the gut lining become compromised or 'open.' This allows material from the gut lumen, such as toxins or proteins, to enter the body, and conversely, body fluids and proteins to enter the lumen, potentially leading to conditions like exudative enteropathy.
Germ-Free Animals (Gnotobiotic)
These are animals bred and raised without any contact with microorganisms. They are born via C-section and fed sterile food in incubators. Studying them reveals the profound impact of the microbiome on gut development, motility, immune system function, and even phenotypes like obesity and anxiety.
10 Questions Answered
The GI system is a tube beginning at the mouth and ending at the anus, designed to digest complex food products into small molecules for absorption while maintaining a protective barrier against the non-sterile lumen.
Communication is bidirectional, involving the vagus nerve, spinal cord, and hormones. The brain acts like a CEO, giving general commands, while the enteric nervous system controls the detailed behavior and reflexes of the gut locally.
The gut primarily feels pain in response to distension or pressure, not cutting. Pain signals are mostly relayed to the brain via the spinal cord through fibers located in the dorsal root ganglia.
The rate at which the stomach empties significantly affects satiety. Protein and fat slow gastric emptying, leading to earlier and longer-lasting satiety compared to saline or simple sugars, which empty much more rapidly.
The varicella zoster virus can establish latency in the enteric nervous system. Upon reactivation, it can kill nerve cells in the gut, leading to conditions like pseudo-obstruction (paralyzed gut) or even perforation, and has been linked to achalasia in the esophagus.
Yes, SSRIs can cause nausea by enhancing serotonin's ability to signal the brain. They also initially speed up gut motility, but over time, they can lead to receptor desensitization and long-term constipation.
The most common cause of leaky gut is allergy, where the immune system reacts and causes the tight junctions between gut epithelial cells to open. This can be triggered by food allergens or other toxins like bee stings.
Most commercial tests that claim to analyze your gut microbiome are not yet useful because they provide insufficient resolution, only identifying broad classes of organisms rather than specific species. This information is not actionable for personalized health interventions.
Fiber provides several health benefits: it can absorb toxins, promote healthy gut motility, and serves as a crucial substrate for colon bacteria. These bacteria digest fiber and produce short-chain fatty acids, which are vital energy sources for colonic epithelial cells.
Taking appropriate probiotics, such as Saccharomyces or certain lactobacilli/bifidobacteria strains, either during or after antibiotic treatment can be helpful. The key is to choose probiotics that are proven to survive passage through the GI tract and colonize the gut effectively.
13 Actionable Insights
1. Avoid Unproven Gut Microbiome Tests
Do not rely on commercial gut microbiome tests or associated supplements, as they often lack sufficient resolution and documented evidence to provide actionable health information, and many are considered a “con.” These tests can lead to abnormally high costs and misguided health decisions.
2. Eat a Balanced, Fiber-Rich Diet
Consume a balanced diet with appropriate nutrients, including fiber, for general health and to support your gut. Avoid extreme or “cleanse” diets, as the microbiome has evolved with humans and cleansing is not beneficial.
3. Prioritize Insoluble Fiber Intake
Incorporate insoluble fiber (e.g., from celery or lettuce) into your diet, as it absorbs toxins, promotes gut motility, and provides essential substrate for beneficial colon bacteria to produce short-chain fatty acids, which energize the colon lining.
4. Prioritize Protein and Fat for Satiety
Consume meals rich in protein and fat to reach satiety sooner and reduce hunger, because these nutrients slow gastric emptying more effectively than salt and sugar.
5. Minimize High-Calorie Liquid Intake
Avoid high-calorie liquids, including alcohol, especially for weight management, as they can bypass the stomach’s satiety signals more easily than solids and undermine efforts to reduce food intake.
6. Choose Solid Foods for Satiety
Opt for solid foods over liquids to promote satiety, as solids delay gastric emptying by requiring mechanical digestion into sub-millimeter particles before passing through the pyloric sphincter.
7. Take Probiotics During/After Antibiotics
Consider taking appropriate probiotics, such as yeast-derived Saccharomyces or lactobacilli/bifidobacteria, during or after a course of antibiotics to help repopulate the gut flora.
8. Select Proven Probiotics
When choosing probiotics, look for products that have demonstrated efficacy and safety through actual tests, such as those regulated by the FTC for specific claims, ensuring the organisms survive transit and provide beneficial effects.
9. Vaccinate Against Shingles (Shingrix)
Get the Shingrix vaccine to prevent shingles reactivation, which can infect the enteric nervous system and lead to severe gut issues like pseudo-obstruction or achalasia, even if the immune system eventually clears the virus.
10. Avoid Dietary Cleanses and Enemas
Do not engage in dietary cleanses or enemas, as they are not beneficial for the body, do not kill bacteria, and can lead to dangerous electrolyte imbalances.
11. Acknowledge Stress-Gut Connection
Be aware that the central nervous system (CNS) can profoundly impact gut function, manifesting as symptoms like “butterflies,” tension-induced diarrhea, or constipation in response to anxiety or fright.
12. Understand SSRI Gut Effects
If taking SSRIs, be aware they can initially cause nausea and speed up gut motility, but may eventually lead to long-term constipation due to receptor desensitization.
13. Diet Won’t Reduce Autism Severity
Do not rely on specific dietary changes to reduce the severity of autism symptoms, as rigorous scientific evidence consistently fails to document a regular or causal relationship, despite anecdotal claims.
6 Key Quotes
The inside of the GI tract is really outside the body. It's internalized external space.
Mike Gershon
The nervous system of the gut is able to function and control reflexes and behavior independently of any influence from the brain or spinal cord. So it is the only nervous system of the body that can work on its own.
Mike Gershon
Most of what's out there on this topic is utter nonsense, commercial tests that promise miracles that don't make any sense and supplements that just don't make any sense.
Peter Attia
If you're fleeing a foxhole because the enemy is coming, it's best if you don't have to stop to defecate along the way.
Mike Gershon
Depression is a potentially lethal illness. And if you've got something in which to treat it, sometimes you just have to use it.
Mike Gershon
The further you get from shore, the deeper the ocean gets.
Peter Attia
2 Protocols
Cholera Treatment
Mike Gershon- Keep track of the patient's water loss by measuring fluid output.
- Replace lost fluids intravenously and orally.
- Add a small amount of sugar (glucose) to the oral rehydration fluid to enhance sodium and water absorption in the small intestine.
Fecal Transplant for C. difficile
Mike Gershon- Administer oral vancomycin as the first-line treatment.
- If the patient does not respond or C. diff recurs, perform a fecal transplant.
- The transplant can be done via enema or an enterocoated capsule containing carefully screened donor stool.