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Endoscopic ultrasound: how it works and why it matters

Dr. Thompson explains endoscopic ultrasound: a scope is placed in the mouth, into the stomach and small bowel, with an ultrasound probe embedded in its tip to see structures just outside the lumen and gain access to them with a needle. It held promise for ablating lesions, and because it goes through a natural orifice rather than opening the abdomen, patients go home the same day and don't feel anything.

The ablation potential is hedged ('maybe').

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Hormonal basics: ghrelin, glucagon, and pre-meal insulin response

Dr. Thompson explains that ghrelin is the hunger hormone produced in the fundus of the stomach; when high, it stimulates hunger by traveling from the gut to the brain. Glucagon's main job is to signal fat burning; it is typically elevated when insulin is low and vice versa. Insulin spikes slightly before eating, and the stomach begins stretching to accommodate the meal before any food is swallowed, potentially triggered by smell, sight, or taste of food (exact mechanism not fully figured out).

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Gene therapy safety, specificity, and rationale for pancreatic targeting

Extensive animal studies used green fluorescent protein to verify the viral vector stays in the tail of the pancreas and does not end up in areas it's not supposed to be; the gene therapy is only active in beta cells, not alpha cells, so expression is limited to where it's needed; the therapy cannot be done in the bowel because bowel cells are not terminally differentiated and turn over every five days, while the pancreas is terminally differentiated, making it a permanent site.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Over 85% of patients in Dr. Thompson's endoscopic therapy practice have been on a GLP-1 and struggled or come off

Dr. Chris Thompson says that in his endoscopic therapy practice, over 85% of patients have already been on a GLP-1 and either struggled on it or come off.

self-reported practice observation

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Obesity phenotyping and precision: do the least intervention needed

Dr. Thompson endorses the goal of moving toward more precision — finding what a patient will respond to and doing the least intervention needed (e.g., if only ghrelin is driving them, just ablate the ghrelin); researchers are actively studying the phenotyping of obesity.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Why the jejuno-ileal bypass failed: blind limb, bacterial overgrowth, and oxalate kidney damage

Dr. Thompson explains the failure modes of the jejuno-ileal bypass: it created a long blind limb with no food passing through, causing bacterial overgrowth; and malabsorbed fat bound calcium in the bowel, so oxalate got absorbed instead and then bound calcium in the body and kidneys, causing renal failure issues.

None stated.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Diet and exercise alone are hard to sustain; Look AHEAD showed modest results

Dr. Thompson notes the Look AHEAD study, which used heavy diet and exercise (including treadmill running), achieved only about 6% total weight loss over 10 years with no improvement in heart disease; diet and exercise alone are hard to sustain for weight loss because the body throws countermeasures (set point) at you.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Natural GLP-1 is rapidly degraded by dipeptidyl peptidase

Dr. Thompson explains the problem with natural GLP-1: you had to infuse it for it to work because it gets chewed up very quickly by dipeptidyl peptidase, and the susceptible N-terminus is the part that binds the receptor, so you can't simply remove it.

Provenance flagged as possible numeric error.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Fermented foods are prebiotic, mildly probiotic, and partially digested — like seeds plus fertilizer for the microbiome

Dr. Chris Thompson explains that fermented foods are prebiotic (feeding the microbiome things it wants), act as a mild probiotic via live cultures like Lactobacillus, are partially digested already, and get the ball rolling for the microbiome like planting seeds plus fertilizer.

explanatory framing with an analogy

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Early colon cancers can be removed endoscopically — organ-sparing surgery with same-day discharge

Dr. Chris Thompson describes that early colon cancers can now be removed endoscopically — called organ-sparing surgery — by removing just the lining where the precancer resides, so patients keep their colon and go home the same day. It's a complicated procedure, but it's easy for the patient.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Gene therapy produces nutrient-responsive GLP-1 and insulin release at the pancreas

With the gene therapy, when you have your meal, the vesicles release GLP-1 and insulin together; making GLP-1 at the pancreas gives it autocrine and paracrine function and is much faster than making it in L cells where it has to travel through the liver.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

NHANES data: only 12% of the population is metabolically healthy

Dr. Thompson cites the UNC NHANES study: less than a third of lean people are metabolically healthy, and only 12% of the whole population is metabolically healthy based on parameters including waist circumference, glucose, and blood pressure.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

The esophagus moves food safely into the stomach; achalasia obstructs this and can be treated by tunneling between its layers

Dr. Chris Thompson describes the esophagus's job as moving food into the stomach safely, with thick linings to handle rougher material. In achalasia — which is not terribly common but becoming more frequent (he sees it every week) — patients feel like food is stuck, with pressure, discomfort, food coming back up, and sometimes needing to induce vomiting. Gastroenterologists can treat it with a procedure that tunnels between the thin layers of the esophagus to cut the muscle and relieve the obstruction.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Food going up the nose after eating signals a possible swallowing problem

Andrew Huberman raises that people sometimes report food seeming to go up their nose after eating (found when blowing the nose), which is not entirely uncommon and can indicate a swallowing problem. Dr. Chris Thompson explains it could be a variety of things, including an oral pharyngeal transfer problem where the hypopharynx transfers food into the esophagus, or high tension in the upper esophageal sphincter.

Andrew Huberman · Best Tools for Gut Health & Weight Loss | Dr. Chris Thompson

Dopamine is about craving and motivation more than pleasure; the mesolimbic pathway is engaged by palatable foods

Most people think of dopamine as pleasure, but dopamine is about craving, wanting, and motivation at least as much and probably more than pleasure. The mesolimbic reward pathway is a midbrain ventral tegmental area to nucleus accumbens dopamine projection. The mesolimbic reward pathway is engaged by palatable foods such as liquid sucrose or high-fat sucrose combinations. Bland-tasting healthy food can engage the dopamine reward pathway when an animal is food-restricted.

well-established neuroscience

Andrew Huberman · How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

Acetylcholine ramps in the hippocampus during active eating

During active eating, acetylcholine levels in the hippocampus ramp up while the animal is holding, chewing, and swallowing food, and ramp down when the animal pauses — measured via fiber photometry.

animal model findings

Andrew Huberman · How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

Sweet taste triggers a cephalic-phase insulin response

Consuming sweet taste triggers a cephalic phase response: insulin is released before nutrients reach the GI tract, preparing the body for the incoming blood glucose perturbation from just the taste of sugar in the mouth.

Andrew Huberman · How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

Childhood obesity and youth type 2 diabetes have risen, with the processed food industry contributing

Overweight children were rare in junior high and high school decades ago, whereas now a noticeable percentage of children and teenagers develop type 2 diabetes. Type 2 diabetes used to be called adult-onset diabetes, but the name changed because children and teenagers now develop it. The highly processed food industry contributed to the rise in childhood obesity and youth type 2 diabetes.

industry contribution stated with hedging

Andrew Huberman · How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

Amnesic patients with hippocampal damage eat multiple meals and cannot interpret satiety signals

Humans with bilateral medial temporal lobe damage including the hippocampus have episodic memory spans of roughly 10 to 40 seconds. In a classic study (attributed to Paul Rosen), densely amnesic patients with hippocampal damage will eat a meal, forget it, and eat a second and even third meal presented by the experimenter. After eating three meals in a row, amnesic patients rate their hunger/satiety around 7 out of 10, showing they receive gut feedback but cannot interpret it without the hippocampus.

classic study findings

Andrew Huberman · How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

Conditioned taste aversion eliminates dopamine responses to sucrose

In conditioned taste aversion experiments, an animal that normally shows dopamine release to sucrose — from a predictive cue or consumption — loses that dopamine response after sucrose is paired with malaise. This is described as the most extreme example of plasticity in the mesolimbic reward system.

Andrew Huberman · How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski