Metagenomics and functional biochemistry: when to combine them

When digestive symptoms are present and it is unclear which test can answer the clinical question, metagenomics and functional biochemistry are not equivalent alternatives: they examine different aspects and may be considered together when each provides relevant information, always with professional interpretation.

In summary:

• Metagenomics analyses microbial genetic material in a sample; functional biochemistry measures substances or products related to biological processes.
• Detecting microorganisms is not the same as measuring the compounds present, and does not, by itself, show that they are responsible for a symptom.
• Combining results can provide complementary information if it addresses a specific clinical question and is interpreted alongside the patient’s history and other data.
• Microbiota and biochemical results are not stand-alone diagnoses and do not prove that a microorganism causes symptoms.

To assess what each approach can contribute, it helps to distinguish the profile of microorganisms from the compounds being analysed. Consult the scope of functional metabolomics before considering a combination of tests.

What is the difference between metagenomics and functional biochemistry?

Metagenomics analyses the genetic material of microorganisms present in a sample, while functional biochemistry measures substances linked to biological processes. They therefore describe different dimensions, and their results are not interchangeable. The microbial activity cannot be inferred automatically from which microorganisms are detected.

In practical terms, the first approach reports microbial genetic signals recovered from the sample; the second reports the substances included in the analysis. Detecting a microorganism does not show that it produced a particular substance, and measuring a compound does not, by itself, identify which microorganism produced it. Interpretation depends on the clinical question and the scope of each method: knowing what is detected is not the same as measuring which substances are present.

For a fuller comparison, see what each analysis can tell you.

What information can each microbiota test provide?

Metagenomics can describe the microbial genetic material detected in a sample, while functional biochemistry can measure specific compounds related to biological processes. What each result tells you depends on the sample, the method, the analytes included and the available evidence for interpreting them.

Detecting a microorganism describes the presence of its genetic material in the sample, but does not prove that it is active, produces a particular metabolite or causes symptoms.

Functional analysis can measure compounds included in its panel, such as short-chain fatty acids. Finding them does not necessarily identify which microorganism produced them or demonstrate a clinical effect.

Before choosing a test, it is worth reviewing the sample, method and analytes it includes. The gut microbiota analysis page provides information on the stated scope of the test. The combined interpretation should address a specific clinical question.

When might it make sense to combine metagenomics and functional biochemistry?

It may make sense to consider both tests when a specific clinical question calls for information on both the microorganisms detected and the biochemical products measured. Combining them is only useful if each result is relevant and a healthcare professional can interpret them alongside the rest of the clinical information.

Before requesting the tests, it is worth defining what question each analysis should help answer and checking that the method and sample are suitable for that purpose. More data do not guarantee a more useful interpretation: if a test does not address the clinical question, its results may be difficult to put into context.

Bringing the results together does not prove that a microorganism produced a compound or that the compound is causing symptoms. Interpretation should take all the findings and a healthcare professional’s assessment into account. To review Xenogene’s integrated profiles, see what information each option includes and whether it fits the question being asked.

What limitations should be considered when interpreting the results?

Metagenomics and functional biochemistry results depend on the sample, the method and the analytes included; on their own, they do not necessarily establish the cause of symptoms. Their interpretation requires clinical context and is not equivalent to a diagnosis, even when both types of analysis are considered together.

Before drawing conclusions, it is worth checking what was analysed and what the report actually measures. Detecting a microorganism’s genetic material does not show that it is causing a symptom; likewise, measuring a compound does not automatically identify which microorganism produced it or determine its clinical relevance.

Interpretation should also take into account the clinical question and other patient information, such as symptoms and medical history. For guidance on what makes a marker useful, see these criteria for selecting biomarkers. The combined interpretation must form part of an assessment by a healthcare professional: combining results does not turn an association into causation.

Frequently asked questions

Does metagenomics show which substances the microbiota produces?

Not on its own: metagenomics analyses microbial genetic material, but does not directly measure the substances present in the sample. To identify specific compounds, a test that includes them is needed. Detecting microorganisms does not automatically show which substances they have produced or in what amounts.

Can functional biochemistry replace a metagenomic test?

These tests are not interchangeable. Functional biochemistry measures specific compounds, while metagenomics studies the genetic material of microorganisms in the sample. Which test may be more relevant depends on the clinical question; the choice should be discussed with a healthcare professional.

Is it always necessary to request both tests?

Not necessarily. Combining them should address a specific clinical question, and each test should provide relevant information to help answer it. Requesting both does not mean their results will establish a cause or be useful in every case; the decision should be individualised.

Who should interpret the results together?

A healthcare professional should interpret the results, taking them into account alongside the clinical history and other relevant information. Reports describe the findings of the tests, but do not by themselves establish what is causing the symptoms or replace clinical assessment.

Explore the profiles that combine the microbiome, function and AI, and consider which option best fits the clinical question.