215 - The gut-brain connection | Michael Gershon, M.D.

KEYPOINTS

• 01

  The gut has its own nervous system: a 'second brain'

  Michael Gershon, a Columbia anatomist and cell biologist who has studied the gut for about 60 years and wrote The Second Brain, explains that the enteric nervous system can run the bowel on its own. When surgeons cut the vagus nerves to treat peptic ulcers, once thought to be psychogenic, the gut kept working. It didn't cure ulcers either, because most are caused by the infection Helicobacter pylori. Peter says this was one of the episodes where he learned the most.

• 02

  A gut with no outside connections still produces a coordinated reflex

  In a very chilly English laboratory at the turn of the 20th century, Bayliss and Starling cut all the nerves to an animal's intestine and raised the pressure inside it. The gut still contracted above the bolus and relaxed below it, a pattern they called 'the law of the intestine'. Seventeen years later, during the First World War, the German scientist Trendelenburg, kept out of the army by tuberculosis, strung a loop of guinea pig intestine on a J-shaped tube in vitro, blew into it, and found the gut 'blew back' in the same coordinated wave, with no brain or spinal cord at all.

• 03

  Rapid cell turnover helps explain why colon cancer is common and small-bowel cancer rare

  The cells lining the gut turn over very rapidly. Gershon links the colon's susceptibility to cancer to the especially frequent turnover of its surface cells. The small intestine absorbs most nutrients and water. The colon mainly conserves sodium (absorbing sodium and secreting potassium) and recovers the final roughly 100 mL a day of fluid. Cholera shows what happens when secretion overwhelms absorption: Gershon says about 3 million people still die from it every year.

• 04

  Gut and brain communicate both ways

  The gut signals the brain through nerves (including stretch and nutrient sensors) and through hormones from enteroendocrine cells, such as cholecystokinin. Some of these are transported across the blood–brain barrier, while glucose is sensed directly in the brain. Most gut hormones reduce appetite. Ghrelin promotes it. Butterflies and stress diarrhoea are this system at work, and Gershon notes that you don't want to stop and defecate when fleeing a foxhole.

• 05

  Gastric bypass works partly by triggering the gut's emergency satiety signals

  Normally, the stomach only lets sub-millimetre particles into the small intestine, because larger loads set off a 'don't do this' alarm. Bypass reroutes food so it reaches the intestine directly. Gershon says this activates that emergency satiety response over and over, which may help explain the rapid, near-universal benefits for obesity and type 2 diabetes.

• 06

  Most of the body's serotonin is made in the gut

  Gershon did his senior thesis on serotonin at Cornell in 1958. Enterochromaffin cells make about 95% of the body's serotonin, and about 80% of the gut's endocrine cells produce it. It also acts as a neurotransmitter in enteric nerves, a growth factor for gut neurons and a trigger of inflammation. SSRIs therefore affect the gut. They cause nausea by amplifying serotonin signals to the brain, speed transit at first and later can cause chronic constipation as receptors desensitize. Gershon adds that depression is potentially lethal, so these risks are often worth taking.

• 07

  Leaky gut is real but usually overused as a term

  The lining has to keep the gut's contents out while letting material move into the gut, which can be dangerous. Gershon says the most common cause of genuine leakiness is allergy, meaning immune hypersensitivity that opens the tight junctions between cells. Severe cases can lose so much protein (exudative enteropathy) that serum albumin falls and the body swells with oedema.

• 08

  Shingles can infect gut neurons

  Gershon and his wife, the virologist Anne Gershon, found that the varicella-zoster virus, which causes chickenpox and shingles, can lie dormant in enteric neurons and reactivate as 'shingles of the gut'. About 15% of shingles sufferers develop postherpetic neuralgia, pain that can persist for years. He calls the newer shingles vaccine, about 97% effective, remarkable, and Peter got his before 50.