Gut barrier & absorption – leaky gut test with calprotectin (stool)

Zonulin is a protein that can loosen the connections between the cells of the intestinal lining (tight junctions). When more zonulin is present, the gut wall can become more permeable (PubMed 21248165). That is why zonulin in stool is measured as a marker of "leaky gut".

Important for interpretation: according to a 2018 study, a widely used commercial zonulin assay does not detect zonulin itself but related proteins such as properdin (PubMed 29459849). The value is therefore an indication, not proof of a permeable gut wall.

Calprotectin comes from white blood cells and rises in stool when the intestinal lining is inflamed (PubMed 31088326). A meta-analysis showed that calprotectin distinguishes chronic inflammatory bowel diseases well from irritable bowel syndrome: a normal value makes such a disease unlikely, but an elevated value does not prove it (PubMed 37823411).

An elevated value can have various causes and should be checked by a doctor.

Alpha-1 antitrypsin is a protein from the blood. If more of it is found in stool, this can indicate protein loss via the intestinal lining, for example with inflamed mucosa (PubMed 20571826).

Secretory IgA (sIgA) is the most important antibody of the mucous membranes; it binds pathogens and foreign substances in the gut (PubMed 21975936). An elevated value can indicate an activated mucosal defence, a low value a weaker one. Laboratories do not assess it uniformly.

In the gut, histamine comes from mast cells in the lining, from histamine-producing bacteria and from food. It is broken down mainly by the enzyme diamine oxidase (DAO) (PubMed 33921522). An elevated value shows that a lot of histamine is present in the gut.

In one study, the gut flora of some people with irritable bowel syndrome produced a lot of histamine, which increased gut pain sensitivity in mice (PubMed 35895832). For the question of histamine intolerance there is the histamine and DAO analysis.

Pancreatic elastase is a digestive enzyme of the pancreas that passes through the gut largely unchanged. A low value in stool can indicate that the pancreas produces too few digestive enzymes (exocrine pancreatic insufficiency). This can show up as fatty stools, bloating, abdominal pain, diarrhoea and unintended weight loss (PubMed 37737818).

The European guideline recommends basing the diagnosis on complaints, nutritional status and a pancreatic function test together (PubMed 39639485). A low value should therefore be checked by a doctor.

The digestive residues show how much fat, nitrogen (from protein), sugar and water remain in the stool. A lot of fat in stool can indicate impaired fat digestion or absorption, for example due to the pancreas, bile acid metabolism or the intestinal lining (PubMed 38429963). A lot of sugar can indicate carbohydrates that were not fully absorbed in the small intestine.

Bile acids help digest fat and are normally recovered in the small intestine. If too many reach the large intestine, this can cause diarrhoea; this bile acid loss is considered common and under-diagnosed (PubMed 26913381).

The intestinal lining is a barrier: it lets nutrients through and holds back bacteria, toxins and undigested food components. "Leaky gut" describes a gut wall that is more permeable than usual. A review lists documented influences including endurance exercise, painkillers from the NSAID group and certain food additives (PubMed 31076401).

Psychological stress is also being studied as an influence (PubMed 36806451). A distinct "leaky gut syndrome" as a diagnosis is not established.

Absorption means uptake: nutrients pass from the gut into the blood. For this to work, they must first be broken down. If breakdown is lacking, for example pancreatic enzymes or bile acids, this is called maldigestion; if uptake through the intestinal lining fails, malabsorption (PubMed 38429963).

The report is structured accordingly: digestive residues, evidence of maldigestion (pancreatic elastase, bile acids) and evidence of malabsorption (calprotectin, alpha-1 antitrypsin).

In research, gut permeability is measured mainly with sugar tests: you drink certain sugars and measure how much of them arrives in the urine (PubMed 31076401). In practice, markers such as zonulin are measured in stool or blood.

This test measures zonulin together with inflammation, defence and digestion markers in stool. It therefore shows several indications of the state of the intestinal lining but cannot prove a permeable gut wall.

No. Increased permeability of the gut wall is well described in conditions such as coeliac disease or chronic inflammatory bowel diseases. A distinct "leaky gut syndrome", however, is not part of medical guidelines. Whether restoring the gut barrier improves complaints has not yet been shown (PubMed 31076401).

Research associates the eleven markers with the following complaints and conditions, with varying strength of evidence:

• Irritable bowel syndrome with abdominal pain, bloating, diarrhoea or constipation: a more permeable gut wall in some patients, observed in studies (PubMed 28404070).
• Chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis: elevated calprotectin, well documented (PubMed 31088326, PubMed 37823411).
• Coeliac disease: increased permeability of the gut wall, well documented (PubMed 31076401, PubMed 21248165).
• Fatty stools, bloating, diarrhoea and unintended weight loss with reduced pancreatic function: well documented (PubMed 37737818).
• Chronic diarrhoea due to bile acid loss: found in up to 40% of people with diarrhoea-predominant irritable bowel syndrome (PubMed 26913381).
• Deficiency of fat-soluble vitamins and malnutrition with impaired fat absorption: described (PubMed 38429963).
• Histamine intolerance with bloating, headache, flushing or itching after histamine-rich meals: described (PubMed 17490952).
• Autoimmune diseases: a link with zonulin is being researched, for example in type 1 diabetes (PubMed 32162764).

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.

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. That complaints improve by restoring the gut barrier has not yet been shown (PubMed 31076401).

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.

The kit contains two sample types: an OmicSnap tube for histamine and two spoon tubes for all other values. The stool must not come into contact with toilet water; a stool collection aid is included. Cooling is not necessary. Only pause prescribed medication after talking to your doctor; if you take painkillers, antibiotics or digestive enzymes, mention this in the results consultation.

Hand in the samples with the completed request form in the shipping box at a post office only from Monday to Thursday, not on Fridays and not in a letterbox.

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.

The gut barrier & absorption test costs €179.90 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 barrier & absorption (€179.90) measures gut barrier, inflammation and digestion without the gut flora. With gut flora, Candida and pH there are the basic gut profile (€285) and the gut profile microbiome & gut barrier (€315). Microbiome Maxi Plus + gut barrier + absorption (€465) combines these values with a molecular-genetic gut flora analysis. For histamine alone there is the histamine stool test (€55).

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