Small Molecules at the Intersection of Health and Microbiota
Metabolon Senior Study Director, Karen DeBalsi, Ph.D., will speak at the 5th Annual European Microbiome Congress. Her seminar titled, “Small Molecules at the Intersection of Health and Microbiota,” will explore how Metabolon’s approach to metabolomics can assess efficacy, monitor toxicity, provide discover biomarkers, measure therapeutic response, determine optimal dosing, gauge non-compliance, and segregate responders from non-responders.
The following Q&A from Kiasko Research provides a preview of her upcoming presentation which will be held on November 13th 2019 at 6pm GMT.
1. For those of our audience who’re new to Metabolon, please can you give us a whistle stop tour of the company’s history and focus?
Metabolon’s comprehensive view of the metabolome reveals the mosaic of functional status of a living system by unlocking inputs such as genes, microbiome and lifestyle. Leveraging one of the world’s most diverse and rich patient data sets, Metabolon is equipped to deliver biologically relevant insights to address some of the most difficult and pressing questions in the life sciences. We help accelerate research and product development success in the biopharma, population health, consumer products, agriculture, wellness and academic research sectors. The company was founded in 2000 and is based in Research Triangle Park, North Carolina with an international headquarters in Germany.
2. We’re looking forward to Metabolon’s presentation at the 5th Annual Microbiome Congress, November 13th – 14th in London - what’ll be the focus of the talk?
The talk will focus on how metabolomics serves as a key technology for microbiome research and unlocking microbiota function in human health. Metabolon’s untargeted view offers the world’s largest knowledge database of more than 5,200 known metabolites. When you can see the entire metabolome, you can fully explore the impact of all environmental and
biologic interactions on a living system.
3. What’s the significance of utilising metabolomics when studying the gut microbiome? Which analytical technologies is
metabolomics replacing and why?
The microbiome has an astounding influence on our health. While other technologies such as 16S ribosomal RNA sequencing yields information on which taxonomic groups are present and at what relative abundance, metabolomics provides researchers with a way to assign function to the microbiota. Metabolites, whether derived from the host or gut bacteria, mediate function within this cross-species relationship. To understand this complex interplay between host and microbiota, researchers need a
technology capable of comprehensively surveying host metabolism, dietaryderived metabolites, xenobiotics, and both novel and canonical metabolites produced by the microbiota. This is exactly what Metabolon’s Precision Metabolomics™ platform does.
4. Can you provide some more detail on Metabolon’s technology and some examples of the clinical applications it’s currently being used in?
Metabolon’s Precision Metabolomics™ technology consists of an unmatched reference library of authenticated metabolites, LC/MS-based platforms that employ a chemocentric approach to accurate metabolite identification, bioinformatics and patented software, a proprietary mLIMS system, quality controls, and a vast institutional knowledge of metabolism. Our Metabolomics applications cover all areas of healthcare and life sciences research, including pharmaceutical R&D, biotechnology and bioprocessing, academic research, population health, precision medicine, nutrition, consumer goods and personal care, and agriculture.
5. How can metabolomics contribute to drug development programs that aim to modulate the gut microbiome?
How a drug is metabolized can significantly affect treatment of disease. These alterations can be performed by both the host and gut microbiota. Metabolomics uniquely provides an accurate and comprehensive assessment of the molecular phenotype that can be used to assess efficacy, monitor toxicity, provide biomarkers, measure therapeutic response, determine optimal dosing, gage non-compliance, and segregate responders from nonresponders. Therefore, it is a productive and cost-efficient route to drug discovery, testing and development.
6. What are the advantages of utilising comprehensive metabolomics technologies vs metabolite profiling or analytical chemistry techniques?
The insight gained by a comprehensive, systematic and accurate assessment of thousands of metabolites far outweighs a technology such as NMR, that can profile less than 50 metabolites. Moreover, even if mass spec techniques are employed, commercially available libraries of metabolites contain significantly fewer entries than found in Metabolon’s propriety library of
approximately 5,200 authenticated biochemicals.
7. Metabolic diseases like Obesity and Type 2 Diabetes are increasing in prevalence year on year. How is Metabolomics playing a
crucial role in improving our understanding of these conditions and progressing dietary interventions and drug development to
These metabolic diseases are multifactorial, affected by genetics, endocrine and environmental influences, and therefore, can be more easily unders tood utilizing metabolomics. For example, several researchers have identified branched-chain and aromatic amino acids as potentially causal factors that can reflect degree of insulin resistance and risk for de veloping type 2 diabetes in individuals. Interestingly, these amino acids are not only obtained from the diet, but their production and bioavailability are modulated by the gut microbiota. Therefore, understanding the relationship of microbial amino acid metabolism to host amino acid homeostasis can aid in the understanding of the pathogenesis and treatment of these diseases.
8. The gut microbiome also plays a significant role in cancer with Jennifer Wargo and Laurence Zitvogel’s work providing some
extremely interesting findings – How can metabolomics aid our understanding of the microbiome’s role in the disease?
Wargo and Zitvogel’s work has focused on the influence of the gut microbiome to the response of checkpoint inhibitors, specifically PD-1 immunotherapy. Both researchers identified significant differences in the diversity and composition of the gut microbiome of responders versus non-responders. Lacking, however, was a mechanism accounting for the immunomodulatory effects of these bacterial differences, which could have been addressed using metabolomics. Though Wargo employed
unsupervised hierarchal clustering of pathway class enrichment predicted by metagenomics, actual measurement of the biochemicals produced in these metabolic pathways providing phenotypic and functional insight was missing. Metabolomics is a tool that allows researchers to move beyond a descriptive analysis of a favourable or unfavourable gut microbiome.
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