Gut-brain axis complete – IBS stool test for neurotransmitters

In the gut, histamine is formed from the amino acid histidine, by mast cells in the lining and by histamine-producing bacteria; it is broken down mainly by the enzyme diamine oxidase (DAO) (PubMed 33921522). The stool value describes how much histamine is present in the gut.

In one study, the gut flora of some people with irritable bowel syndrome produced particularly large amounts of histamine; in mice colonised with this flora, gut pain sensitivity increased (PubMed 35895832). Whether an elevated value contributes to your complaints cannot be read from this. For the question of histamine intolerance there is the histamine and DAO analysis.

Tryptophan is an amino acid that the body cannot make itself and takes in with food. It is the only precursor of serotonin and in the gut is also broken down via the kynurenine pathway and by bacteria into indoles (PubMed 31825083).

Changes in the kynurenine pathway have been described in functional gut complaints such as irritable bowel syndrome (PubMed 34576297). A low value in stool can have many reasons, such as diet or bacterial breakdown; it says nothing about how much serotonin is produced in the brain.

Serotonin is an important signalling substance in the gut: special cells of the intestinal lining (enterochromaffin cells) produce it, triggering gut movement and secretion and passing signals on to the nervous system (PubMed 17241888). Several approved IBS medicines act on serotonin receptors.

In irritable bowel syndrome, changes in the serotonin system have been described, for example in the serotonin transporter of the intestinal lining (PubMed 34362210). Whether a single stool value is meaningful for this has not been established. Antidepressants from the SSRI group can influence the value.

GABA (gamma-aminobutyric acid) is the most important inhibitory messenger of the nervous system and also occurs in the gut; certain gut bacteria can produce GABA (PubMed 36144440).

In one study, people with diarrhoea-predominant irritable bowel syndrome had lower GABA levels in the blood and an altered GABA system in the intestinal lining compared with controls (PubMed 29852727). Overall, the role of GABA in irritable bowel syndrome is still little researched (PubMed 34362210).

Irritable bowel syndrome is a common disorder of gut-brain interaction: recurrent abdominal pain together with altered bowel habits, i.e. diarrhoea, constipation or both alternating (PubMed 33049223). Worldwide, about 4–9% of people are affected depending on the criteria (PubMed 32702295).

Mechanisms include altered gut movement, increased gut sensitivity and altered processing in the brain; changes in the gut flora and mucosal defence are less well documented (PubMed 33049223, PubMed 28404070).

Gut and brain are in constant exchange via nerves such as the vagus nerve, hormones, the immune system and messengers; gut bacteria influence the production and breakdown of such messengers (PubMed 36144440). Stress can thus affect the gut, for example the gut barrier (PubMed 36806451).

Tryptophan metabolism is considered a link between the gut flora and the brain (PubMed 31825083). Much of this comes from animal studies; how strongly these pathways act in humans is still open.

No. Irritable bowel syndrome is identified from the complaints according to the Rome criteria and a targeted medical work-up; with warning signs, further tests are needed (PubMed 33049223). A stool value that is actually used in the work-up is calprotectin: it helps to rule out a chronic inflammatory bowel disease (PubMed 37823411).

Histamine, tryptophan, serotonin and GABA in stool are research markers. They describe the gut but neither provide an IBS diagnosis nor rule out other diseases. Calprotectin is included, for example, in the gut barrier & absorption test.

Only to a very limited extent. Serotonin and GABA in stool come from the gut, from cells of the intestinal lining and from bacteria. Serotonin from the gut does not reach the brain, which produces its own serotonin.

The values therefore show what happens in the gut, not the state of mood or mental health. For messengers and their breakdown products in urine there is Neurotransmitter Plus; this measurement does not provide a diagnosis either.

Research associates the four values with the following complaints, with varying strength of evidence:

• Abdominal pain and cramps with diarrhoea, constipation or both alternating, typical of irritable bowel syndrome: changes in the serotonin and GABA systems described but little researched (PubMed 33049223, PubMed 34362210).
• Bloating and distension: common accompanying complaints in irritable bowel syndrome (PubMed 33049223).
• Increased gut pain sensitivity: bacterial histamine as a possible factor in some patients, so far shown mainly in animal studies (PubMed 35895832).
• Complaints after histamine-rich meals such as headache, flushing or diarrhoea: described in histamine intolerance (PubMed 17490952).
• Mood, sleep and perceived stress: links via the gut-brain axis and tryptophan metabolism are being researched (PubMed 31825083, PubMed 36806451).

These are associations from studies, not causes in an individual. A stool test cannot explain complaints and does not provide a diagnosis. Persistent complaints should first be checked by a doctor.

With blood in the stool or black stool, unintended weight loss, fever, diarrhoea at night, severe or new abdominal pain, persistent vomiting or difficulty swallowing, the first step is a doctor's practice, not a self-test. The same applies if your bowel habits change for the first time from around age 50 or if bowel cancer, coeliac disease or chronic inflammatory bowel disease runs in the family.

Irritable bowel syndrome is a diagnosis made only after a medical work-up (PubMed 33049223).

If mood, drive or sleep are clearly affected for weeks, talk to your GP. In an acute crisis, the German TelefonSeelsorge helpline is available free of charge around the clock on 0800 111 0 111; in an emergency, call 112.

If you suspect coeliac disease, do not stop eating gluten before the medical work-up, because the tests may otherwise come back falsely normal. A stool test does not replace bowel cancer screening.

This page does not give treatment recommendations. Whether a result means anything at all and which steps make sense depends on your overall situation: complaints, previous findings, medication and diet. Medical treatment of irritable bowel syndrome is based on the complaints (PubMed 33049223).

What makes sense for you belongs in a conversation with the ORY expert team or with your doctor or naturopath, for example from the ORY expert network. The results consultation is included in the price.

Antibiotics should have been stopped 4 weeks before sampling. List your current medication on the request form, especially probiotics, antihistamines and antidepressants (SSRIs), because they can influence serotonin, histamine and GABA. Never stop prescribed medication without talking to your doctor. You do not need to fast.

A morning stool is ideal. The stool must not come into contact with toilet water or cleaning agents; insert the sampling lance in at least 4 places and swirl the tube, do not shake it. Hand in the sample at a post office only from Monday to Thursday; store samples taken on a Friday in the fridge until Monday.

Analysis usually takes 7–21 days from the arrival of the sample at the laboratory. As soon as your report is ready, we let you know. A results consultation with the ORY expert team is included in the price.

Gut-brain axis complete costs €116 including VAT, shipping, return postage and results consultation.

Statutory health insurance in Germany generally does not cover stool analyses you order yourself. With private insurance, reimbursement may be possible; how it works is described under "Reimbursement by private insurance".

Gut-brain axis complete (€116) measures four messenger markers in stool. The metabolome (€380) adds the microbiome, tryptophan breakdown products, bile acids and gut barrier markers. Inflammation and digestion markers such as calprotectin and pancreatic elastase are measured by gut barrier & absorption (€179.90); gut flora, leaky gut and histamine together by the basic gut profile (€285). For histamine alone there is the histamine stool test (€55), for messengers in urine Neurotransmitter Plus (€185.90).

Which scope makes sense for you can be clarified in the free initial consultation.