In recent years, there has been an explosion of microbiome research, fuelled by easier access to next generation sequencing (NGS) technologies. As such, an ever-growing number of studies claim to have found links between the composition of the microbiota and various states of health and disease.

While a limited number of commercial products exist for microbiome standardisation, there are currently no certified or accredited reference reagents available to the wider community. Additionally, it is known that different methods can produce very different results even when the same sample is being analysed. This has led to a reproducibility crisis in the field.

The use of global standards has the potential to solve this problem as it would lead to improved method development, making it easier to compare findings from across the world and preventing the reporting of inaccurate conclusions.

How is the NIBSC helping?

The NIBSC have produced two DNA reference reagents, Gut-Mix-RR and Gut-HiLo-RR, which consist of mock communities of 20 common gut microbiome strains present in different proportions. Additionally, a reporting framework has been developed to capture four key measures of microbiome health.

The analysis of sequencing data generated from these reference reagents has confirmed that they can be used to accurately evaluate the performance of different bioinformatics pipelines and reveal their biases.

Dr Gregory Amos, Microbiome Section Head at the NIBSC, who is leading this work comments that:

“Currently, we cannot accurately compare results between microbiome studies as the methods differ so widely across laboratories. This is particularly worrying as there are over 900 clinical trials investigating the microbiome and its role in disease. These reagents are the first step in addressing reproducibility in the microbiome field. We have a lot more reagents in the pipeline which will be released over the next 12 months.”

Both Gut-Mix-RR and Gut-Lo-RR will be made available from the NIBSC in October 2020.

What are the next steps?

Following these encouraging results, the reagents will now be the focus of an international collaborative study designed to test whether they are fit to serve as highest order WHO International Reference Reagents. This work will involve multiple expert laboratories and is due to take place later this year with the hope that the reagents will receive WHO endorsement in October 2021. If you are interested in participating in this study, please contact us.

These reagents are the first step in addressing reproducibility in the microbiome field. We have a lot more reagents in the pipeline.

Dr Gregory Amos, Microbiome Section Head at the NIBSC

These reagents represent only the first part of a broader strategy for effective microbiome standardisation being carried out by the NIBSC. Whole cell reagents, to control for biases in DNA extraction, and matrix-spiked whole-cell reagents, to control for biases from inhibitors or storage conditions, will also be developed to complement the DNA standards for downstream analyses.

It is hoped that the widespread adoption of these standards and the associated reporting system will help to harmonise research from the microbiome field and ultimately make it easier for the most promising therapies to enter the clinical arena.

This work is funded by the NIHR Policy Research Programme (NIBSC Regulatory Science Research Unit) and Innovate UK. Further information about our microbiome research can be found here.