The Microbiome

Metabolomics: Looking Beyond Which Bacteria Are There

Microbiome analysis can tell us which microorganisms are present, but metabolomics helps researchers look at what is happening within the gut environment. By measuring small molecules and microbial products, it offers a different view of biological activity.

Science explainer

Metabolomics: Looking Beyond Which Bacteria Are There

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Science explainer

Focus

Metabolites, microbial activity and gut function

What can metabolites reveal beyond bacterial names?

Knowing which microorganisms are present in the gut is important.

But it leaves another question unanswered:

What are those microorganisms actually doing?

Microbial communities are metabolically active.

They use nutrients and other substrates, interact with one another and produce a wide range of chemical compounds.

Some of those compounds can be measured.

Metabolomics is the study of these small molecules — known as metabolites — and can provide another layer of information about activity within the gut ecosystem.

Rather than asking only “who is there?”, metabolomics helps researchers ask “what is happening?”

How do researchers identify and measure metabolites?

Metabolomics uses analytical techniques to identify and measure small molecules within biological samples.

These samples can include blood, urine, intestinal contents or faeces.

Two commonly used analytical approaches are mass spectrometry and nuclear magnetic resonance spectroscopy.

Researchers can either target specific metabolites they are already interested in or use broader, untargeted methods designed to detect a much wider range of compounds.

The resulting profile can contain molecules originating from several sources.

Some come from the dog's own metabolism.

Some come directly from food.

Some are produced or transformed by microorganisms.

Others may result from interactions between the host, diet and microbiome.

This complexity is precisely what makes metabolomics useful — but also why careful interpretation is important.

Which kinds of gut metabolites can be measured?

Metabolomic studies can examine many different types of molecules.

Short-chain fatty acids

These are produced during microbial fermentation of certain substrates and include compounds such as acetate, propionate and butyrate.

Amino-acid metabolites

Microbial metabolism of proteins and amino acids can produce a wide variety of compounds.

Bile acid metabolites

Gut microorganisms can modify bile acids produced by the host, creating additional metabolites within the intestinal environment.

Lipid-related compounds

Dietary and host-derived fats can also contribute to the metabolic profile.

Hundreds or even thousands of additional molecules may be detected in untargeted studies.

The overall pattern can therefore provide a chemical snapshot of activity within a biological system.

Why can metabolite and microbiome changes differ?

One of the most important lessons from metabolomics is that changes in microbial composition do not always tell the whole story.

A relatively small change in which microorganisms are present can sometimes be accompanied by a larger change in the metabolites detected.

Conversely, differences in microbial composition do not necessarily mean that microbial function has changed to the same degree.

This reflects an important feature of microbial ecosystems.

Different microorganisms can sometimes perform overlapping metabolic functions.

The nutritional environment matters too.

The compounds produced by microbial communities depend partly on which substrates are available to them.

Metabolomics therefore provides a useful bridge between diet, digestion, microbial activity and the wider gut environment.

How does metabolomics complement microbial sequencing?

Metabolomics expands the way we can investigate the microbiome.

Microbial sequencing asks:

Which microorganisms are present?

Metabolomics asks:

Which compounds are present?

Together, these questions can provide a richer picture.

If the microbiome changes, metabolomics can help researchers investigate whether the chemical environment changes alongside it.

And if digestion changes which nutrients reach microbial communities, metabolomics may help reveal differences in the compounds produced downstream.

That gives us a useful sequence:

Digestion → Substrate → Microbial activity → Metabolites

It is one reason modern microbiome research increasingly looks beyond bacterial abundance alone.

To compare metabolite profiling with a method for identifying bacterial groups, read our guide to 16S analysis.

What can metabolite measurements leave uncertain?

Metabolomics provides powerful information, but identifying a metabolite does not always reveal exactly where it came from.

The same compound may be produced by the dog, by microorganisms, or by both.

Diet can also contribute metabolites directly.

A metabolite measured in faeces represents the amount remaining at the end of the digestive tract, not necessarily the total amount that was produced. Some may already have been absorbed or transformed elsewhere.

Results can also be affected by sample collection, storage and analytical technique.

For that reason, metabolomic data are most informative when interpreted alongside diet, microbiome composition and other measurements rather than in isolation.

Sources and further reading

References

Further reading:

Pilla R, Suchodolski JS. The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease. Frontiers in Veterinary Science. 2020;6:498.

Wernimont SM, Radosevich J, Jackson MI, et al. The Effects of Nutrition on the Gastrointestinal Microbiome of Cats and Dogs: Impact on Health and Disease. Frontiers in Microbiology. 2020;11:1266.

Nicholson JK, Lindon JC. Systems biology: Metabonomics. Nature. 2008;455:1054–1056.

Deng P, Swanson KS. Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges. British Journal of Nutrition. 2015;113:S6–S17.

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