Mast cells: alarm cells in the gut, histamine and the disputed MCAS

Healthy state

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. are immune cells that settle at the body's boundaries: skin, airways and particularly densely beneath the gut lining, often right next to nerve endings. They are filled with granules containing 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”, the enzyme tryptase, prostaglandins and other messengers.

They are the tissue's alarm system. In response to a worm, a toxin or an injury, they release their granules within seconds. Histamine makes blood vessels leaky, stimulates mucus production and gut movement, and attracts more immune cells. In the gut, this helps flush out intruders.

They are triggered in several ways. In a classic allergy, IgE antibodies IgE The antibody of classic allergy. It sits on mast cells and triggers their alarm on contact with the allergen. More in the chapter “Allergies and intolerances: how the gut learns to tolerate food” sit on their surface and react to a particular protein. But they also respond to messengers from nerves, to stress hormones such as CRH, to bacterial substances and to some medications.

Histamine from food and histamine from mast cells are two different things. The enzyme DAO DAO (diamine oxidase) An enzyme in the gut wall that breaks down histamine from food before it reaches the blood. More in the chapter “DAO: the enzyme that intercepts histamine from food” breaks down histamine from food in the gut. Mast cells, by contrast, release histamine directly in the tissue, where it meets nerves and blood vessels. A low-histamine diet changes little about this second source.

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. More in the chapter “The gut-brain axis”, one study found more mast cells in the colon lining than in healthy people in 34 of 44 patients. The closer the activated mast cells lay to the nerve fibres, the stronger the abdominal pain. Other studies found smaller or no differences, and a large study showed that the mast cell count varies so much in healthy people that counting them in gut samples does not allow a diagnosis.

A particularly interesting mechanism: in mice, a gut infection together with a food protein triggered a local allergy, only in the gut and not measurable in the blood. Later, the same protein caused abdominal pain via IgE, mast cells and histamine. In people with IBS, injecting gluten, wheat, soy or milk protein into the gut lining led to swelling and mast cell activation. This could explain why some people react to certain foods after a gut infection.

Stress also acts via mast cells. In a study of healthy people, giving a public speech and the stress hormone CRH made the small intestine more permeable. A mast cell stabiliser prevented both. This is a direct link between head, mast cells and gut barrier.

This must be distinguished from mast cell activation syndrome Mast cell activation syndrome (MCAS) A rare condition with repeated attacks caused by mast cell messengers in several organs. The diagnosis needs lab evidence during an attack. , MCAS for short. The expert consensus requires three things at once: typical attacks in several organs, such as flushing, hives, a drop in blood pressure or diarrhoea; lab proof during an attack, ideally a rise in blood tryptase of at least 20 per cent plus 2 ng/ml above one's own baseline; and improvement with drugs against mast cell messengers. Genuine MCAS is rare.

In recent years many people have received the diagnosis without this evidence, often together with joint hypermobility (hEDS) and a racing heart on standing up (POTS POTS Postural orthostatic tachycardia syndrome: the heart rate rises by at least 30 beats per minute on standing without a drop in blood pressure, with light-headedness and exhaustion. More in the chapter “POTS and hypermobility: when circulation and connective tissue drag the gut along”). A review found no reliable studies for a shared mechanism of these three. The US allergy society and the authors of the consensus warn that other, treatable causes are overlooked this way.

One reason for raised baseline tryptase levels is hereditary: 4 to 6 per cent of the population have a raised baseline level, usually due to extra copies of a tryptase gene (hereditary alpha-tryptasemia). In families with this condition, flushing, IBS, circulatory problems and hypermobile joints were more common.