IgA: the antibody that keeps the gut clean, and what vitamin A, D and omega-3 have to do with it

The body makes more IgA than all other antibodies combined, most of it in the gut. How it is made, why vitamin A matters for it, and what vitamin D and omega-3 really contribute.

How solid is the research? Promising

How IgA is made in the gut and what it does is well researched, mainly in mice. That a genuine vitamin A deficiency weakens the gut's defences is certain. That extra vitamin A, D or omega-3 improves IgA in people who are well supplied is not proven.

Cause or consequence? Cause and consequence

IgA is the border police of the mucosa. It is missing under stress and low variety — and then opens the door for allergies and germs.

Healthy state

Immunoglobulins are antibodies, proteins that recognise germs and foreign substances. There are five classes: IgG in the blood, IgM as an early response, 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” in allergies, IgD and IgA (secretory IgA) The antibody of the mucous membranes. It is released into the gut in large amounts, where it holds germs in the mucus without causing inflammation. . IgA is the antibody of the mucous membranes. The body makes more of it than of all the others combined, and most of it ends up in the gut.

It is made by plasma cells directly beneath the gut lining. The gut cells have a transporter that takes up IgA on the back side, carries it right through the cell and releases it on the inner side. A piece of the transporter stays attached to the IgA as a protective coat. This produces secretory IgA, which also withstands digestive enzymes.

Inside the gut, IgA works not like a weapon but like a bouncer. It binds bacteria, viruses and toxins, clumps them together and holds them in the mucus so that they do not reach the cells. In doing so it causes hardly any inflammation. Many harmless gut bacteria are coated with IgA; this binding helps shape who lives where in the gut.

This is where vitamin A comes in. Certain immune cells in the gut's lymph nodes convert vitamin A into retinoic acid. In mice, retinoic acid gave newly activated immune cells a kind of postcode for the gut, and together with other messengers it drove B cells to make IgA. Mice without vitamin A lacked the IgA-producing cells in the small intestine. With retinoic acid, the same cells also promote regulatory T cells, which tolerate harmless food.

For IgA to form, the microbes themselves are needed. Bacteria in the gut stimulate IgA production, partly with the help of T cells (precise, directed against particular bacteria), partly without them (broader, faster). The body makes IgA in two subtypes: one more in the small intestine, which is more precise, and one in the large intestine, which is more resistant to the bacteria's digestive enzymes. Saliva, tears, breast milk and the airways also contain sIgA; in the mouth it keeps the oral flora in balance.

Even babies receive IgA through breast milk. In mice that received no maternal IgA, certain bacteria in the small intestine temporarily multiplied strongly, and the immune system remained more prone to inflammation into adulthood.

Plasma cells beneath the lining make IgA, and the gut cells carry it inside. There it holds germs in the mucus. Vitamin A helps build this up.

Disrupted state: causes and effects

IgA deficiency is the most common inborn antibody deficiency. Most affected people notice nothing, because IgM takes over part of the work. Some have more frequent respiratory infections, allergies, Autoimmune disease A disease in which the immune system attacks the body's own tissue, for example the thyroid in Hashimoto's or the pigment cells in vitiligo. More in the chapter “Autoimmune diseases and the gut: Hashimoto's, vitiligo, type 1 diabetes and more” or gut problems. In people with IgA deficiency, researchers found more potentially problematic bacteria in the stool, fewer beneficial species and more species that normally live in the mouth and throat.

This is particularly important for Coeliac disease An autoimmune disease in which gluten damages the lining of the small intestine. It is diagnosed with a blood test and usually a biopsy while you are still eating gluten. More in the chapter “Lactose, fructose, gluten: making sense of intolerances”: the usual blood test measures IgA antibodies against tissue transglutaminase. If you make hardly any IgA, the result is falsely negative. That is why total IgA should also be measured with the test.

IgA also shows what the immune system is paying attention to. In mice and in stool samples from people with Inflammatory bowel disease Umbrella term for Crohn’s disease and ulcerative colitis: long-term, relapsing inflammation of the gut that needs medical treatment. More in the chapter “Immune system and inflammation”, it was precisely the bacteria most heavily coated with IgA that triggered gut inflammation in germ-free mice. This is a research tool, not an everyday test.

Apart from inborn deficiency, IgA defences can also decline temporarily. With long-lasting strain, such as chronic stress, very hard endurance training or lack of sleep, it is discussed whether sIgA in saliva falls and infections become easier. The findings are not consistent, though, and a single value in stool or saliva allows no conclusions for the individual. In old age and in malnutrition the defences of the mucous membranes are also often weaker. The most important consequence: if you are repeatedly plagued by infections, look for the cause, not for a stool value.

A genuine vitamin A deficiency is rare in rich countries but common in poorer regions. There, vitamin A supplements in children between six months and five years reduced overall mortality and mortality from diarrhoea by about 12 per cent each and made diarrhoea less frequent. This fits its role in the gut's defences.

But it does not follow that more helps. Preformed vitamin A (retinol) can build up in the body. EFSA sets 3000 micrograms a day as the upper limit for adults, mainly because of birth defects in pregnancy. For vitamin D, the upper limit is 100 micrograms (4000 IU) a day. No convincing study was found showing an effect of vitamin D or omega-3 on gut IgA in humans.

Without IgA, germs get closer to the wall, and species from the mouth settle more easily.

Where it comes from and where it leads

The same symptoms can have different roots. This map shows what may be involved in this problem and what may follow from it.

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Connections, not certainty: a link means “can”, not “must”. What applies to you is best clarified in a talk with your doctor.

What often helps

Lifestyle

Diet, exercise, sleep, social contact and dealing with stress.

Vitamin A from food Preformed vitamin A is found in liver, eggs, dairy products and fish, and its precursor beta-carotene in carrots, sweet potatoes, pumpkin and green leafy vegetables. If you eat a varied diet, you are usually well supplied. According to EFSA, people stay below the upper limit if they eat liver and offal at most once a month; anyone pregnant or planning a pregnancy should avoid liver products altogether. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1][2]
Breastfeed if possible Breast milk provides secretory IgA, which helps shape the early gut flora. The link with later protection has mainly been shown in mice. Breastfeeding is recommended for many reasons; if you cannot breastfeed, you should not blame yourself for it. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [3]
Feed variety so the defences stay practised IgA is stimulated by gut bacteria, and a diverse flora supplies more stimuli. Varied plant-based food with fibre and fermented foods is therefore the obvious route, even though a direct effect on IgA has not yet been shown in humans. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [4]

Natural supplements

Supplements do not replace a medical check-up. Discuss dosage and interactions with your doctor or pharmacist.

Vitamin A only for a deficiency For a proven deficiency or in regions where deficiency is common, vitamin A is well supported. With a normal diet, an extra supplement brings nothing for the gut's defences according to current knowledge, but it can do harm. The upper limit for adults is 3000 micrograms of preformed vitamin A a day; in pregnancy only after consulting a doctor. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [2][1]
Vitamin D: correct a deficiency, no more Vitamin D plays a part in the immune system, but an effect on gut IgA has not been shown in humans. In IBS, the studies on vitamin D are mixed. A deficiency can be measured and corrected; the upper limit is 100 micrograms (4000 IU) a day. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [5][6]
Omega-3: interesting, but not proven for IgA In small studies, omega-3 fatty acids change the composition of the gut flora, for example more butyrate producers. Whether this affects IgA production has not been studied. Oily fish once or twice a week is a sensible approach; a capsule specifically for IgA is not. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [7]

Medical treatments

Information, not a treatment recommendation. Decide together with a doctor. Approval and availability differ from country to country.

Measure total IgA with the coeliac test The guideline recommends measuring total IgA together with the transglutaminase antibodies. With IgA deficiency, IgG-based tests are used. Important: do not eat gluten-free before the test. Established How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [8]
Check for IgA deficiency with frequent infections If you have conspicuously frequent respiratory infections, recurring gut infections such as Giardia or several autoimmune diseases, you can have your blood immunoglobulins measured. There is no IgA replacement; the consequences are treated. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [9][10]
Be critical of stool tests for secretory IgA Some labs offer “sIgA in stool” as a marker of mucosal defence. No study was found showing that the value improves diagnosis or treatment. The values vary a lot, for example with stress and infections. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Check your vaccination protection If you make little IgA or often have infections, you benefit especially from up-to-date vaccination protection. Ask your doctor which vaccinations are recommended in your country. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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How we rate the evidence

Trust score 5 of 5:Established: Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies.
Trust score 4 of 5:Well supported: Several randomised studies in humans with largely consistent results.
Trust score 3 of 5:Promising: Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies.
Trust score 2 of 5:Plausible: Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms.
Trust score 1 of 5:Experimental: Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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