Microbiota, microbiome and metabolome: three words that are constantly confused

In today's health conversation, the words "microbiota," "microbiome," and "metabolome" are increasingly being used by scientists, doctors, probiotic manufacturers, and social media influencers. The problem is that these terms are often used interchangeably.

Yes, this is a mistake, and not just a terminological one. Behind each of these concepts is a separate level of biological organization.

The idea of ​​this post is to simplify the understanding of these concepts so much that they are simply not confused.

Microbiota is a collection of living microorganisms that inhabit a certain ecological niche, whether it's ours or another environment, and we can obtain them in a cultivated form (i.e. grow them in laboratory conditions) using various technological methods, even if these cultivation methods are extremely complex, and this is especially true for microorganisms that are extremely sensitive to oxygen.

So, we all have our own unique personalized intestinal microbiota, skin microbiota, oral mucosa, respiratory and genitourinary tract microbiota.

Importantly, these are not just bacteria, as is often thought, but also archaea, microscopic fungi, and other microorganisms, including viruses.

You can learn more about this here:

Borrel G, Brugère JF, Gribaldo S, Schmitz RA, Moissl-Eichinger C.

The host-associated archaeome.

Nature Reviews Microbiology. 2020;18(11):622–636.

 https://doi.org/10.1038/s41579-020-0407-y

One of the most authoritative reviews, emphasizing that archaea are an integral component of the microbiota of humans and other organisms

Berg G, Rybakova D, Fischer D, et al.

Microbiome definition re-visited: old concepts and new challenges.

Microbiome. 2020;8:103.

https://doi.org/10.1186/s40168-020-00875-0

This work clearly distinguishes between the concepts of microbiota (a collection of microorganisms) and microbiome (microorganisms together with their genomes, metabolites, structural components, and habitat).

Baker BJ, De Anda V, Seitz KW, et al.

Diversity, ecology and evolution of Archaea.

Nature Microbiology. 2020;5:887–900.

 https://doi.org/10.1038/s41564-020-0715-z

The human microbiota includes not only bacteria, but also archaea, microscopic fungi, protists, and viruses, which together form the body's complex microbial ecosystem.

So, the microbiota answers the basic question: who is present in a particular microbial community?

However, the list of microorganisms alone does not provide a complete picture of the state of this community. Two people may have a similar set of bacterial genera, but differ significantly in their ratio, activity and interaction with the body.

The concept of microbiome  is broader.

Its definition varies somewhat in the scientific literature. In a narrow sense, the microbiome is the collection of genetic material of microorganisms. In a broader, ecological sense, it is the microbial community together with its genes, functions, interactions, and habitat.

In other words

The microbiome includes not only bacteria, as is often believed, but also archaea, microscopic fungi, viruses, protists, as well as their genomes, mobile genetic elements, extracellular nucleic acids, and products of their vital activity (i.e., all living microorganisms and non-living, metabolic products) (including viruses and nucleic acid fragments).

The most cited publication that offers a modern definition of the microbiome is the full bibliographic reference (Vancouver):

Berg G, Rybakova D, Fischer D, Cernava T, Champomier-Vergès MC, Charles T, et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome. 2020;8(1):103. doi:10.1186/s40168-020-00875-0.

It is in this work that the authors note that the concept of microbiome encompasses not only microorganisms (bacteria, archaea, fungi, protists, and viruses), but also their “theatre of activity,” which includes:

1. structural components of cells;

2. metabolites;

3. signaling molecules;

4. mobile genetic elements;

5. extracellular nucleic acids and other products of interaction with the host.

To confirm that archaea are an integral component of the human microbiome , one can also cite:

Borrel G, Brugère JF, Gribaldo S, et al. The host-associated archaeome. Nature Reviews Microbiology. 2020; 18:622–636. https://doi.org/10.1038/s41579-020-0407-y

That is, the microbiome allows us to ask a more difficult question: what is this community potentially capable of doing?

For example, the microbial genome may contain genes necessary for the conversion of food components, the synthesis of certain vitamins, the metabolism of bile acids, or the formation of biologically active compounds.

But it's important to understand the limit here: the presence of a gene does not mean that it is necessarily active right now .

Genetic information indicates potential. For its realization, appropriate conditions are required: available nutrients, a certain level of acidity, interaction with other microorganisms, the state of the intestinal barrier, the rate of transit of intestinal contents and many other factors. The physiological environment of the intestine can significantly affect both the composition of the microbial community and its metabolic activity.

Metabolom

This is a collection of low-molecular-weight substances, or metabolites, that are contained in a biological sample at a specific point in time.

Metabolites are the final or intermediate products of biochemical processes. They include, in particular, organic acids, amino acids, lipid compounds and other molecules that can participate in the regulation of metabolism, immune reactions and intercellular communication.

At the same time, the metabolome cannot be considered exclusively a product of the microbiota. Some molecules come with food, some are synthesized by human cells, and some are formed as a result of the joint metabolism of the organism and microorganisms.

Therefore, the metabolome no longer answers the question "who is there?" or "what can they do?", but the question: what is really happening in this system right now?

The metabolome includes:

• short-chain fatty acids (acetate, propionate, butyrate);

• secondary bile acids;

• tryptophan metabolites (indoles);

• polyamines;

• amino acids;

• organic acids;

• vitamins;

• neuroactive compounds (GABA, serotonin, dopamine precursors, etc.).

You can find more about this here.

Nicholson JK, Holmes E, Kinross J, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–1267.

Wishart DS. Metabolomics for investigating physiological and pathophysiological processes. Physiological Reviews. 2019;99:1819–1875.

Why is this difference important?

Because the microorganisms in our bodies are not a static list of names. They are a living system that constantly responds to nutrition, medications, age, stress, physical activity, and health status.

Knowing who lives in this system is important, but not enough. It is equally important to understand what this community is capable of doing and what substances are formed as a result of its interaction with the human body.

That is why health cannot be explained by the presence or absence of a single “good” or “bad” bacterium. What matters is how the entire microbial ecosystem works and what dialogue it establishes with our body.

So, let's remember:

microbiota is the composition of a microbial community that can be cultivated;

microbiome – its genetic and functional potential;

Metabolome is the actual biochemical result of the entire system.