Microbiota and the immune system – what research says about this link

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The slogan “immunity starts in the gut” appears on thousands of packages. It is based on a true anatomical observation, but marketing has stretched it far beyond what research shows. Below we separate three layers: anatomical facts, results of animal studies and what researchers have observed in humans.

Why the gut is linked to immunity at all

Lymphoid tissue of the digestive tract

The wall of the digestive tract contains a large amount of lymphoid tissue, known as GALT (gut-associated lymphoid tissue). It includes Peyer’s patches, single lymphoid follicles and cells spread through the mucous membrane.

There is a practical reason for this. The digestive tract is a large surface that is in contact with the environment. Food components and microorganisms reach it all the time, so the mechanisms of recognition and tolerance need to work exactly there.

Popular texts often repeat that 70 or 80 per cent of immune cells are in the gut. This is an estimate that people quote without naming the original source, and counting methods differ. So it is safer to talk about a large part of the lymphoid tissue than about an exact percentage.

The gut barrier

The second element is the gut barrier. It is a set of structures that separates the inside of the gut from the body’s tissues: a layer of mucus, a single layer of lining cells joined by tight junctions, and immune cells under this lining.

It has two jobs at the same time: it lets the body absorb food components and it limits the passage of unwanted elements. It is a dynamic system, and how tight it is changes under the influence of many factors.

“Leaky gut”, a term that is popular on the internet, is not a clinical diagnosis. However, scientists do study how permeable the gut barrier is, and they have described changes in it in various diseases.

More: Gut microbiota – how it develops and what shapes it throughout life

What studies in animal models show

Most data about mechanisms come from studies in mice, including animals raised in sterile conditions, which means without microbiota. This model cannot be recreated in humans, which limits how far the conclusions can be applied to people.

In animals without microbiota, researchers described less developed lymphoid tissue in the digestive tract, fewer Peyer’s patches and a different production of antibodies in the mucous membrane. After microorganisms were introduced into the gut, some of these differences became smaller. The results depended on the species of microorganisms used (Chung et al., 2012).

In vitro studies are a separate group. They are carried out on cell cultures outside the body. They describe how single types of cells react in conditions without blood circulation or a response from the whole body.

Conclusions from both types of studies have the same limit. They show that gut microorganisms take part in the development of immune structures in animals. But they do not tell us what happens in a healthy person.

What researchers have observed in humans

In this area, studies in humans are mostly observational. They describe how a certain make-up of the microbiota occurs together with laboratory results or clinical conditions in the groups studied.

There were also intervention studies. In these, researchers gave specific strains or changed the diet and measured selected immune parameters. These studies include small groups and use different designs, which makes them hard to compare.

A separate area is observations about the link between the make-up of the microbiota and the response to vaccines. These are early data. They describe statistical links, not a cause-and-effect mechanism.

The legal situation is clear. The list of claims permitted by Regulation (EU) No 432/2012 has no claims about the gut microbiota or microbial products in relation to the immune system.

More: Why a supplement producer cannot promise treatment – health claims in practice

Why these observations do not lead to a simple practical conclusion

Correlation is not causation

We need to say this clearly, because it is the most common mistake in texts on this subject. An observational study may show that people with a certain make-up of the microbiota more often have a certain immune parameter. This does not mean that one causes the other.

There are three possible explanations for the same observation: the microbiota affects the parameter, health affects the make-up of the microbiota, or both come from a third factor, for example diet, age or medicines.

To answer the question, we need intervention studies with a suitable size and design. There are few such studies, and the ones we have look at specific strains and groups, not at the whole category.

Immunity is not one single thing that you can increase

The second problem is the idea itself. The immune system is not a slider that you can move up. It is a set of mechanisms with different jobs: recognition, tolerance, immune memory and regulation.

This is why the sentence “something boosts immunity” has no exact meaning. A change in a single laboratory result is not the same as better protection against infection. Some reactions of the immune system are even stronger in unwanted conditions.

It is also worth saying clearly: the studies described here do not show that the make-up of the microbiota affects how often a particular person gets infections. No such link has been shown at the individual level.

How to read adverts that mention immunity

For food and supplements, there is a simple rule: companies can only use permitted claims, only for the components they were permitted for, and only when the amount conditions are met.

Wording on the packagingWhat it means under the law
An authorised claim for a component, for example “vitamin C contributes to the normal function of the immune system”A claim from the list of permitted claims, when the amount conditions are met
“Boosts immunity”, “for immunity” without naming a componentA general phrase that is not a claim from the list
“Supports the microbiota”, “rebuilds the gut flora”There are no permitted claims about the microbiota
A reference to studies without naming the strain or type of studyYou cannot judge what the result is about and in whom it was found
A picture of immune cells or a shieldA visual element, not information about the product’s properties

The example in the first row of the table is an authorised health claim for vitamin C, included in Regulation (EU) No 432/2012. Similar claims have been permitted for vitamins A, D, B6, B12, folic acid, and for zinc, selenium, iron and copper, among others.

They apply to the nutrients named, not to the microbiota or the product as a whole. A product can only use them if a portion contains a significant amount of the nutrient.

What we can honestly say

In a few sentences, it looks like this:

  • Anatomy. A large part of the lymphoid tissue is linked to the digestive tract. This is an established fact.
  • Animal models. In animals without microbiota, researchers described less developed immune structures in the digestive tract.
  • Studies in humans. The data are mostly observational, and there are few intervention studies, all with small groups.
  • Practical conclusion. Studies have not shown that the make-up of the microbiota affects how often a single person gets infections.
  • The law. There are no permitted health claims that link the microbiota with the function of the immune system.

This is a valid and active area of research, but it is at an early stage. The same care applies to other popular topics about the gut.

More: The gut-brain axis – where the term second brain comes from

Summary

The link between the digestive tract and the immune system has a solid anatomical basis: the lymphoid tissue of the digestive tract and the gut barrier are well described. This fact is behind the slogan “immunity starts in the gut”.

The next levels of this idea are much weaker. Data about mechanisms come mainly from animal models and in vitro studies, and observations in humans show correlations only.

In practice, this means that phrases about boosting immunity have no exact meaning. Permitted health claims do not support them, except for the nutrients named in the law and only in the exact wording that the law sets.

FAQ

Do supplements boost immunity?

This phrase has no exact meaning and is not a permitted health claim. The law only allows claims from the list, for example the statement that vitamin C contributes to the normal function of the immune system, and only for products that contain a significant amount of this component. This is not a recommendation to use any product. It only describes the law.

Does diet affect the immune system?

A lack of nutrients is a known health problem, and for some nutrients there are permitted claims about the normal function of the immune system. But correcting a lack of a nutrient is one thing. Saying that diet changes immunity in a person without any lack of nutrients is something else. If you have questions about your health, talk to a doctor.

Will a microbiota test tell me something about my immunity?

No. There are no reference values that link the result of such a test to the state of one person’s immune system. The result only describes the make-up of the sample at the time it was taken.

Where does the number of 70 per cent of immune cells in the gut come from?

It is an estimate that popular texts repeat, usually without naming the original study, and counting methods differ. It is safer to say that a large part of the lymphoid tissue is linked to the digestive tract.

Sources

  1. Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods.
  2. Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods, other than those referring to the reduction of disease risk and to children’s development and health.
  3. Hill C., Guarner F., Reid G. et al., Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic, Nature Reviews Gastroenterology & Hepatology, 2014, vol. 11, no. 8, pp. 506-514.
  4. Berg G., Rybakova D., Fischer D. et al., Microbiome definition re-visited: old concepts and new challenges, Microbiome, 2020, vol. 8, no. 103.
  5. Marco M.L., Sanders M.E., Gänzle M. et al., The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods, Nature Reviews Gastroenterology & Hepatology, 2021, vol. 18, no. 3, pp. 196-208.
  6. Belkaid Y., Hand T.W., Role of the microbiota in immunity and inflammation, Cell, 2014, vol. 157, no. 1, pp. 121-141.
  7. Chung H., Pamp S.J., Hill J.A. et al., Gut immune maturation depends on colonization with a host-specific microbiota, Cell, 2012, vol. 149, no. 7, pp. 1578-1593.

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