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Microbiome and molecules - Novel methodologies for exploration

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Published on Tuesday, 21 December 2021

In an article recently published in the journal ISME Communications, researchers from the Systems Ecology group of the Luxembourg Centre for Systems Biomedicine (LCSB) at the University of Luxembourg present a novel methodology to systematically characterise the molecules secreted by the human gut microbiome using multi-omics technologies. This publication is the first outcome of the ExpoBiome project supported by the European Research Council (ERC) Consolidator Grant awarded to Prof. Paul Wilmes in 2019. Thanks to these new results and with the quality criteria for multi-omics data defined in another article published in Nature Medicine in November, the methodological basis is now set for ExpoBiome.

A complex mixture of microbiome-secreted molecules

The human gut microbiome – the community of microorganisms inhabiting our gastrointestinal tract – plays an important role in health and disease. Through the numerous molecules they secrete, these microorganisms can influence human metabolism, ensure intestinal homeostasis and stimulate the immune system. Over the last decade, technical advances – such as high-throughput sequencing – have allowed researchers to gather more insights into the gut microbiome’s structure and function. Nevertheless, the complex mixture of microbiome-secreted molecules, which includes nucleic acids (DNA and RNA), proteins and metabolites, has so far eluded systematic study.

A large majority of these molecules do not have any references in scientific databases: for example, between 40% and 70% of genes found in the gut microbiome encode proteins of unknown function. For small molecules, the percentages are even much greater. “The diverse collection of molecules secreted by the gut microbiome remains completely unexplored,” details Prof. Paul Wilmes, head of the System Ecology group. “As a result, most properties of the microbiome are yet to be understood.”

Illustration by Dr Valentina Galata.

Extracting, isolating and analysing

To be able to better study these properties, researchers from the Systems Ecology group developed a new methodological framework, optimised for the extraction of intracellular and secreted molecules from flash-frozen stool samples collected from healthy human individuals. It allows the scientists to isolate different factions from one sample and to use specialised integrated multi-omics analyses to systematically characterise microbiome-derived molecules. With further adjustments, this new methodology will also become applicable to other sample types such as saliva or vaginal swabs.

This new methodology will help researchers to investigate the links between specific microorganisms and some of the molecules found in the human gut, and to explore the impact these microbiome-secreted molecules have on human physiology. “With the integration of additional omics data, we will be able to gather more information on the diversity and function of the microbiome,” explains Bianca De Saedeleer, first author of the article. “For example, we hope to better understand how the molecules produced by the microorganisms can modulate inflammatory pathways in chronic diseases.”

Building a new framework for microbiome research

While the methodology established by the LCSB researchers lays the foundation for the systematic study of the gut microbiome’s molecular complex, another recent publication is defining new quality criteria for human microbiome research as a whole. A multidisciplinary group of researchers, including Prof. Wilmes, adapted existing guidelines and developed new elements tailored to microbiome studies. They created STORMS, a 17-item checklist that provides guidance for concise and complete reporting of these studies. It will facilitate manuscript preparation, peer review and comparative analysis of published results.

“The interdisciplinary nature of human microbiome research – that spans epidemiology, biology, bioinformatics, ecology, translational medicine and statistics – makes both developing new methodologies and reporting of results a challenge. Thanks to these recent advances, we now have a complete framework for the ExpoBiome project,” concludes Paul Wilmes.


The ExpoBiome project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 863664).

This work was supported by the Luxembourg National Research Fund (FNR) (CORE/16/BM/11333923 and CORE/15/BM/10404093).