A huge number of microorganisms live in the human gut. This is not just an interesting fact. For more than ten years, it has been an area of intensive research. At the same time, many simplifications have grown around it: from out-of-date numbers to conclusions that the studies do not support. Below, we explain what is known about the microbiota, how researchers study it and where the limits of this knowledge are.
Microbiota and microbiome – two terms that do not mean the same
Popular texts sometimes use both words as if they were the same, but they mean different things. The microbiota is the group of microorganisms that live in a specific environment, here the digestive tract: bacteria, archaea, fungi, viruses and protozoa.
The microbiome is a wider term: it covers the microbiota together with the genetic material of these organisms and the conditions of their environment. An international position paper from 2020 made this definition clearer and removed differences in the scientific literature.
In practice, the microbiota answers the question “who is there”, and the microbiome also answers the question “what these microorganisms can do”. This matters when you read publications, because studies that sequence genes describe the microbiome, not just a list of species.
Two popular expressions need a comment. Calling the microbiota a “second genome” or a “forgotten organ” is a metaphor from journalism, not a scientific term. The microbiota is not an organ in the anatomical sense, and it is not the human genome.
How the microbiota develops in the first years of life
The perinatal period
Microorganisms start to settle in the digestive tract in the perinatal period, and this happens step by step. The factors that studies describe include the type of birth, the type of feeding, exposure to antibiotics and the newborn baby’s environment.
At this time, the microbiota of a baby has little variety and changes easily. Studies describe a majority of groups of bacteria linked to the breakdown of milk components, which reflects the food that is available to them.
It is important to note that much of the data on the effect of perinatal factors comes from observational studies. This means that they describe things that happen together, not cause and effect.
The first years and the introduction of new foods
When a child starts to eat solid foods, the composition of the microbiota clearly changes. Complex carbohydrates and fibre are new substrates, that is material to process, and this helps bacteria that can break them down.
The scientific literature accepts that the variety of the microbiota grows in the first years of life, and its composition becomes closer to the profile seen in adults. The speed of this process varies.
This does not mean that there is one pattern of normal development of the microbiota. Children differ a lot, and the limits of what is typical are still being studied.
The microbiota in adults
Relative stability and its limits
In adults, studies describe the composition of the microbiota as relatively stable. The main groups of microorganisms stay for long periods, and the changes are more about proportions than a complete change of composition.
This stability has limits. Changes in diet, medicines, diseases of the digestive tract or moving to a new place can shift the proportions of different groups. Some of these changes are temporary, and some last longer.
Differences between people are also important. Two healthy people can have a clearly different microbiota. This is why studies compare groups more often than individual people.
A separate question is how well the microbiota resists disturbance and how fast it returns to its starting state. Both differ between people and are hard to predict.
Read more: The microbiota after antibiotic treatment – what research says and what to ask your doctor
What affects the composition of the microbiota
Diet
Diet is the best documented factor, because it provides the substrates that microorganisms process. What matters most is the intake of components that are not digested in the upper part of the digestive tract, including fibre and resistant starch.
Intervention studies are studies where researchers change one factor on purpose. In these studies, researchers saw changes in composition after a change in diet. The changes can be fast, but they can also be temporary: when people go back to their earlier diet, the composition moves back towards its starting state.
The products of the fermentation of these components, including short-chain fatty acids, are among the most often measured values in this type of study.
Read more: Short-chain fatty acids (SCFA) – what research on the microbiota says about them
Medicines
The best described example is antibiotics, which by definition act on microorganisms. After their use, studies observe changes in variety and in the proportions of groups. The speed of return to the state before treatment varies.
Research also covers medicines other than antibacterial ones. A screening study of more than a thousand medicines showed that about a quarter of the medicines targeting human cells stopped the growth of at least one gut strain in the laboratory. Separate studies are needed to show what these observations mean in clinical practice (Maier et al., 2018).
Take antibiotics only as your doctor advises. Do not draw any conclusions about treatment from these observations.
Read more: What has a negative effect on the gut microbiota – diet, stress, medicines, sleep
Age
The composition of the microbiota changes over a lifetime, and the differences are both in variety and in the proportions of groups. Studies have described different profiles in babies, children, adults and older people.
These differences are hard to interpret, because age comes together with many other factors: diet, the number of medicines, other diseases and physical activity. To separate the effect of age alone, researchers need specially designed studies.
Environment and lifestyle
One factor that studies describe is where people live. Populations from different regions of the world show clear differences, and researchers link them mainly to different diets.
Observational studies have also described links between the composition of the microbiota and physical activity, contact with animals, smoking and sleep quality. These are correlations: they show that things happen together, but they do not show which is the cause and which is the effect.
This point applies to a large part of media reports about the microbiota. The statement “people with feature X had a different microbiota” is not the same as the statement that the microbiota causes this feature.
Is there one normal microbiota?
This section is important, because the answer is: there is no such pattern, and you should not assume that there is one.
Researchers have tried to put this variety in order. In 2011, they suggested enterotypes, that is repeated types of microbiota composition. The idea started a wide discussion, and later studies showed that the borders between these types are not clear and depend on the method of analysis.
Today, there is no agreed definition of a “healthy microbiota” as a specific set of species. People more often talk about features of the community, such as variety or the ability to return to the starting state after a disturbance. But even these values have no clear reference ranges.
This has a direct practical result. It is hard to compare the result of a commercial microbiota test with a norm, because there is no widely accepted norm for an individual person. Such a result describes the state of the sample, not a difference from a standard.
How researchers study the microbiota
| Method | What it can show | Limit |
|---|---|---|
| Microbiological culture | Properties of living strains, possibility of further studies | Many gut bacteria are hard to grow in a laboratory |
| 16S rRNA gene sequencing | Composition of the community at genus level, less often at species level | Limited resolution, no information about functions |
| Metagenomics | The set of genes in the sample, functional potential | High cost, complex analysis, potential is not activity |
| Metatranscriptomics | Which genes are active at a given moment | Unstable material, the result depends on the time of sampling |
| Metabolomics | Compounds in the sample, including bacterial metabolites | It is hard to link a compound to a specific microorganism |
The big change in methods came with the development of sequencing. Large projects that have listed the genes of gut microorganisms since about 2010 showed a variety that culture methods could not detect.
Limits of current methods
This section is as important as the list of methods, because without it, it is easy to read too much into the results.
- A stool sample is not the whole gut. The composition of the microbiota differs along the digestive tract and between the inside of the gut and the mucus layer. A stool test mainly describes the last part of the gut.
- Potential is not activity. If a gene is present in a sample, this does not mean that it is active. Metagenomics describes functional potential, not what really happens.
- The method affects the result. How the sample is collected and stored, how the genetic material is isolated and which analysis tools are used all change the result. This makes it hard to compare publications.
- No reference values. There are no set normal ranges for individual groups of bacteria in one person.
- Changes over time. The result describes the state at the moment of sampling, and the composition of the microbiota also changes in the short term.
What science knows and what it does not know
The description is relatively well documented: which groups of microorganisms live in the gut, how their composition changes over a lifetime and what happens together with this composition. Studies have also described the metabolic pathways that bacteria use to process the substrates that reach the gut.
Conclusions about causes and effects are much less certain. A large part of reports about the microbiota comes from observational studies. They show that a certain composition happens together with a certain condition, but they do not show the direction of the link. There are fewer intervention studies with people, and they often include small groups.
This also applies to areas that the media often write about, such as links between the microbiota and the nervous or immune system. These are areas of research where most detailed observations come from animal models and in vitro studies.
Read more: The gut-brain axis – where the term second brain comes from, Microbiota and the immune system – what research says about this link
It is also worth noting the legal situation. The list of health claims authorised by Regulation (EU) No 432/2012 has no claims about shaping or restoring the gut microbiota. So such wording cannot be used in communication about foods and food supplements.
Read more: Postbiotics – what they are and how they differ from probiotics and prebiotics
Summary
The gut microbiota starts to develop in the perinatal period. It changes clearly in the first years of life when a child starts to eat new foods. In adults, it stays relatively stable, but changes in diet, medicines and living conditions can affect it.
There is no single pattern of normal composition that you could compare the result of one test with. Healthy people differ a lot, and attempts to sort these differences into repeated types are still under discussion.
Research methods have developed a lot, but they have limits. They mainly describe the last part of the gut, more often potential than activity, and they have no reference values. So when you read reports about the microbiota, check whether they come from observational or intervention studies. And remember that things that happen together do not prove cause and effect.
FAQ
How many microorganisms live in the human gut?
The popular statement that bacterial cells outnumber human cells ten to one has been revised. Estimates published in 2016 show that the numbers are similar, roughly one to one. These are estimates with some uncertainty, and they depend on the assumptions used.
Can I test my microbiota?
Commercial microbiota tests are available, but it is hard to interpret the result. There are no widely accepted reference values for an individual person, and the result describes the state of the sample at the moment of sampling. If you have concerns about your health, talk to a doctor. Do not rely only on the result of such a test.
Does a change in diet change the composition of the microbiota?
Intervention studies observed changes in composition after a change in diet. These changes were sometimes fast, but also often temporary. The size of the response differs between people, so the same diet does not have the same effect on everyone.
Why do reports about the microbiota sometimes contradict each other?
There are several reasons: different methods of sampling and analysis, small study groups, large differences between people and more observational studies than intervention studies. With such methods, different results are expected. They are not a sign of a mistake.
Sources
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- Sender R., Fuchs S., Milo R., Revised estimates for the number of human and bacteria cells in the body, PLoS Biology, 2016, vol. 14, no. 8, e1002533.
- Qin J., Li R., Raes J. et al., A human gut microbial gene catalogue established by metagenomic sequencing, Nature, 2010, vol. 464, no. 7285, pp. 59-65.
- Arumugam M., Raes J., Pelletier E. et al., Enterotypes of the human gut microbiome, Nature, 2011, vol. 473, no. 7346, pp. 174-180.
- Koh A., De Vadder F., Kovatcheva-Datchary P., Bäckhed F., From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites, Cell, 2016, vol. 165, no. 6, pp. 1332-1345.
- Gibson G.R., Hutkins R., Sanders M.E. et al., Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics, Nature Reviews Gastroenterology & Hepatology, 2017, vol. 14, no. 8, pp. 491-502.
- 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.
- Maier L., Pruteanu M., Kuhn M. et al., Extensive impact of non-antibiotic drugs on human gut bacteria, Nature, 2018, vol. 555, no. 7698, pp. 623-628.