The gut-brain axis

Healthy state

Gut and brain are connected by five routes. First, nerves: the vagus nerve Vagus nerve The tenth cranial nerve and the most important nerve of the rest-and-digest system. It connects the brainstem and the abdominal organs; most of its fibres tell the brain what is happening in the gut. More in the chapter “The vagus nerve: the data line between belly and head” as the “cable” between belly and brainstem, and the enteric nervous system, the “belly brain” of several hundred million nerve cells in the gut wall, which largely controls movement and secretion on its own. Second, hormones, above all the stress axis with cortisol and the hormone cells of the gut. Third, messengers of the immune system. Fourth, substances made by gut bacteria, such as short-chain fatty acids Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. More in the chapter “Butyrate and other short-chain fatty acids”, bile acid Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea” derivatives and breakdown products of protein building blocks. And fifth, mast cells Mast cells Immune cells beneath the skin and mucous membranes, filled with histamine and other messengers. They raise the alarm in allergies, infections and stress. More in the chapter “Mast cells: alarm cells in the gut, histamine and the disputed MCAS” and other immune cells that sit right next to nerve endings in the gut wall. Most signals travel from the gut to the brain, not the other way round.

One example is serotonin. Most of the serotonin in the body is made by hormone cells in the gut wall, where it controls gut movement, fluid release and nausea. This serotonin is not the “mood substance” of the brain: it barely crosses the blood-brain barrier, and the brain makes its own. What is exciting is that in mice, hormone cells in the gut form direct contact points with vagus fibres and can report sugars or nutrients to the brain within fractions of a second, faster than through the blood.

Normally this stream is filtered. The brain assesses every signal: is it important or background noise? Descending pathways from the brain to the spinal cord dampen gut signals, just as you stop hearing a clock ticking after a while. Consciously, we notice only hunger, fullness, bloating and the urge to go. Attention, expectation, mood and earlier experience constantly adjust this filter. That is why the same stretch feels different when eating with friends than when alone before an exam.

What role gut microbes play is a field with big promises and small proof. In mice, a particular Lactobacillus changes behaviour and stress response, but only when the vagus nerve is intact. This shows that the route exists, not that the same effect occurs in humans. In humans, the links between microbiome Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity”, mood and gut sensitivity are mostly correlations: differences are seen, but often it is not known what is cause and what is consequence.

Disrupted state: causes and effects

In IBS Irritable bowel syndrome Recurring abdominal pain linked to bowel movements, without tests finding another cause. Today it is understood as a disorder of gut–brain interaction. and related conditions it is mainly the processing that is disturbed. Experts now speak of disorders of gut-brain interaction. There are two dials. At the gut itself the nerve endings become more sensitive (“peripheral sensitisation”); in affected people the gut wall contains more activated mast cells close to nerves, and in one study pain intensity was related to this. In the brain the filter weakens (“central sensitisation”): signals that normally stay below awareness are felt as pain or pressure. This is called visceral hypersensitivity. The gut is not “broken”; it reports too loudly.

Stress turns both dials. In a small study of healthy people, the stress hormone CRH made the small intestine more permeable via mast cells and changed gut movement, and the vagus nerve, which normally calms, was less active in IBS in some studies, as measured by heart rate variability. This mainly concerned subgroups, such as women or people with depression; on average, most studies found no clear difference (more in the chapter on the vagus nerve). In addition, tension stiffens the abdominal wall and pelvic floor, and shallow breathing does not exactly support digestion.

The opposite direction is just as important. Ongoing abdominal symptoms make you tired, anxious and low; inflammatory messengers alone can cause a feeling of illness and low mood. Anyone who fears the next flare avoids food, travel and appointments, watches the belly constantly and sleeps worse, and all of this sets the filter even more sensitively. For many the cycle begins with a trigger such as a gut infection, a course of antibiotics or a stressful phase of life. Why it stays in some people and not in others is not settled.

For microbes, too, there are hints but no certainty. In a mouse study, gut bacteria from the stool of people with IBS triggered abdominal pain via histamine Histamine A messenger substance of the body that is also found in aged and fermented foods. Too much can cause headache, flushing or diarrhoea. More in the chapter “Histamine intolerance: much searched, little proven” and mast cells. This is a possible mechanism, but not yet a proven treatment approach in humans. What is certain is only that the composition of the gut flora in IBS is on average somewhat different from healthy people, without a uniform pattern.

Three misunderstandings are common. “Psychosomatic” does not mean “imagined”: the symptoms are real and have measurable foundations. “It’s only in the head” is just as wrong, because gut, immune cells and microbes are involved. And “if the tests are normal, nothing is there” is false: normal endoscopies and blood tests rule out serious disease, not a disorder of function. That is why you can work on the gut and the head at the same time, and that is exactly what the best treatments do.