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The importance of incorporating metabolomics into your microbiome research

Metabolomics is important in understanding systems biology and clinical research regarding various diseases. [1] According to an article in BioTechniques,

“Metabolites are considered to ‘act as spoken language, broadcasting signals from the genetic architecture and the environment,’ and therefore, metabolomics is considered to provide a direct ‘functional readout of the physiological state’ of an organism.”

Why is metabolomics the last piece of the ‘omics’ puzzle? It is because of our failure to appreciate the significance of metabolic alterations in an organism and our lack of technological advances to analyze the metabolome. [1] 

As a product manager focused on novel product development in the microbiome space, I have followed the recent multi-omics trends, spoken with key industry leaders and learned the importance of metabolomics integration with the microbiome.

I interviewed four industry leaders in metabolomics and asked them why they thought incorporating metabolomics into microbiome studies is important:

  • Jason Bush (R&D scientist) from MSPrebiotics – a company that specializes in high quality prebiotic powder for a healthy gut;
  • Julian Marchesi from Imperial College London – a professor who specializes in molecular microbial ecology;
  • Lisa Freinkman (staff scientist) and Greg Michelotti (Scientific Director of Biology) at Metabolon, Inc – a company that specializes in metabolomics discovery and research solutions.

In this blog, I will share their answers and thoughts on metabolomics and the microbiome.

Why do you think it is important to incorporate metabolomics into microbiome studies?

Dr. Lisa Freinkman and Dr. Greg Michelotti from Metabolon, Inc.

“Over the last decade, DNA sequencing technologies have provided a wealth of data on microbiome composition across numerous human populations and disease states, yet an understanding of what exactly makes a person’s microbiome ‘healthy’ or ‘diseased’ has remained elusive in most cases.

Missing from the puzzle have been small-molecule metabolites, which are the primary language of communication between microbes and their hosts. We have already seen multiple discoveries of microbial metabolites that impact human physiological functions, such as bacterial-produced amino acid and bile acid metabolites that modulate the host immune system. Given the diversity of bacterial metabolism – which far outstrips that of mammals – and the myriad effects that the microbiome can exert to promote either health or disease, these examples are likely just the tip of the iceberg. While DNA sequencing can give us a roster of the players that make up the microbiome, metabolomics can provide key insights into what those players are doing in vivo.”

Dr. Jason Bush from MS Prebiotics

“Interpreting the health consequences of microbiome changes is confounded by redundancies in the metabolic capacities of various microbes and the important role that ecological context seems to play.  Obtaining metabolomic data provides an opportunity to mechanistically understand how inputs like prebiotics are being utilized by the microbiome and, ultimately, how they are affecting the host.”

Dr. Julian Marchesi from Imperial College London

“There are two major axes via which commensal microbes communicate with the host, the proteome and metabolome. While the taxonomic data is noisy and very variable between individuals, the metabolic axis is much more conserved, but still shows variability.  For example, we all have the microbial capacity to make short chain fatty acids, but some people make high amounts and some make low amounts.”

What is the future of metabolomics research?

Dr. Lisa Freinkman and Dr. Greg Michelotti from Metabolon, Inc.

“Clearly, in order to generate true biological insights, it is critical not only to measure many metabolites across many subjects, but to do so with the highest possible reproducibility, sensitivity and confidence in metabolite identification. This applies in all research contexts, but in none more so than in the microbiome, because it is in the microbiome that both the chemical diversity of metabolites and the heterogeneity across subjects are particularly high.

Encouragingly, consensus in the field is now emerging on key issues, such as the importance of authentic chemical standards and of specific data quality control metrics, which should improve the reliability and comparability of metabolomics data moving forward. We believe the next frontier will be to tap the unexplored chemical diversity of the microbiome – that is, to discover new metabolites in a way that is rapid, data-driven, and scalable.”  

Dr. Jason Bush from MS Prebiotics

“I see metabolomics research complementing microbiome studies to help explain the differences between microbiome intervention ‘responders’ and ‘non-responders’, with respect to various physiological parameters.  We hope this information can be used to develop consortia of microbiome interventions to transform ‘non-responders’ into ‘responders’.”

Dr. Julian Marchesi from Imperial College London

“We have been investing in the metabolic axis space for over 10 years and it is a corner stone of our work into different microbiomes, since we believe that it is a major route by which microbes influence the host’s physiology.”

What healthcare challenges can metabolomics research solve?

Dr. Lisa Freinkman and Dr. Greg Michelotti from Metabolon, Inc.

“Metabolomics is an indispensable discipline for healthcare research because, at the simplest level, metabolites are small molecules, as are most drugs. For example, studying metabolomics can lead directly to the discovery of metabolic enzymes – whether human or bacterial – that can readily be targeted with small-molecule drugs to treat a particular disease. Within microbiome research, metabolomics can provide much-needed clarity on the mechanism by which a particular microbial strain or community exerts its effect on our health. Ultimately, that may mean a patient can be treated with beneficial metabolites – small-molecule chemicals that are relatively easy to characterize and mass-produce – rather than with live bacteria that may pose safety and quality risks.

More broadly, metabolomics represents a vast and mostly unexplored space of human heterogeneity. Integrating genetics, gene expression, and environmental influences as well as the activity of our commensal microbes, the metabolome could hold the key to many questions that have not been fully resolved by genomics. Specifically, leveraging the language of the metabolome to decipher the microbiome could answer such questions as why certain therapeutics only work for some patients, why certain individuals are more susceptible to disease, and why different people respond differently to the same foods and lifestyle choices.”

Dr. Jason Bush from MS Prebiotics

“It’s hard to imagine healthcare challenges that could not benefit from metabolomics research!”

Dr. Julian Marchesi from Imperial College London

“Using metabolite profiling can overcome the inherent variability in the species and strains found in the gut and other microbiomes and focus in on the agents of change.” 

Interested to learn more about metabolomics and microbiome? Have any questions about where to start?

Send us an email info@dnagenotek.com or to hello@metabolon.com and we will be happy to answer your questions on metabolomics.

References:

[1] https://bitesizebio.com/31115/importance-metabolomics/

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