Chemicals in our bloodstream are more powerful than you think! Precision medicine, once a concept of science fiction, has now become a reality in healthcare, allowing for personalised disease diagnosis and treatment tailored to the unique characteristics of your body.
So, what is metabolomics? It is defined as the comprehensive and systematic analysis of "metabolites" in the human body via specimens such as blood or tissue samples. Metabolites are products of metabolism, usually small molecules such as sugars, organic acids, amino acids, lipids, and nucleotides. Read on to find out more!
Overview
Precision medicine, which has also been called personalised medicine or individualised medicine, is when healthcare aims to design interventions to prevent disease or improve clinical care strategies to achieve bespoke health for everyone. Science has proven that variability in environment, lifestyle, genes, or every molecular pattern in human bodies impacts the chances of disease and the outcomes of treatment. Therefore, the science of analysing those factors has emerged in many fields, including genomics (about genes), transcriptomics (about gene transcription, such as RNA), proteomics (about proteins in cells, from gene expression), and metabolomics. The suffix "omics'' is used to describe those various fields of quantification of biological molecules, as mentioned.
Metabolomic studies emerged both in humans and plants after more than 25 years of development. However, talking about metabolomics and metabolites is not a new concept of using chemical tests to deal with health conditions. For instance, the glucose strip test has been used to detect and evaluate patients with diabetes for more than half a century.1,2 Then, several tests have been developed to detect molecules resulting from complex biochemical pathways.
Basic concepts in metabolomics
The most simplified concept of metabolomics is to study small molecule metabolites and how they interact with biological systems in our body, called human metabolomes. Types of those molecules include sugars, lipids, amino acids, fatty acids, nucleic acids, or other chemical compounds. Metabolites in the human body, including metabolic intermediates and terminal products, are registered to be around 220,000 in 2022, and 22,600 of some specific metabolites are linked with diseases. They are commonly classified as endogenous metabolites and exogenous metabolites, depending on whether they were produced in the human body or not. In plant metabolomics, the classification is mainly primary and secondary metabolites, which are the metabolites produced to maintain routine plant function or other ecological functions, respectively.
Getting information about those metabolites requires a process called metabolic profiling to identify and quantify the metabolites. The important part is that when metabolism in the human body is so complex and varied over time, including its numerous biochemical reactions, the metabolomics data must be enormous. In the first decade of development, there were limitations to analytical techniques as they could only take cross-sectional or “snapshot” data at a certain time. Since 2015, real-time metabolic profiling has been continuously developed in plants and microorganisms. Novel technologies enable scientists to analyse chemical reactions in metabolic pathways precisely, resulting in a better understanding of metabolic reactions.3
Techniques and methods in metabolomics
The procedures of metabolomics aim to obtain biological samples from humans or organisms, then extract the metabolites and analyse them as metabolomics data. The common pipeline for the procedures consists of 4,5,6
- Design an experiment to scope the field of the experiment and eliminate the chance for error. They usually categorise the field into targeted metabolomics, which is specifically identified, and untargeted metabolomics, which are unspecified and broad types of compounds, in order to compare across samples and generate new hypotheses.
- Sample preparation involves obtaining samples from sources such as plants, bacteria, or human secretions, e.g., urine, blood, plasma, or faeces.
- Extraction, mostly by chromatography, is the chemical process of extracting small molecules that contain various soluble attributes. The most common techniques are gas chromatography and liquid chromatography.
- Profiling by mass spectrometry (MS) or nuclear magnetic resonance (NMR), which are technologies used for detecting small molecules, results in massive amounts of data on the types and quantities of metabolites.
- Data processing, metabolomics analysis, and interpretation: the metabolomics data would be processed from spectrometry signal interpretation and noise optimisation and derived into statistical data. Various databases provide techniques and metadata for future metabolomics analyses.
Applications of metabolomics
Metabolomics studies would have a large impact on human health.
- Plant metabolomics will enable us to improve crop productivity by understanding their growth and plant disease prevention.
- Bacteria, microorganisms, or other organisms will make humans understand their activities and lead to infection prevention.
- In particular diseases, metabolomics leads us to discover novel disease biomarkers and helps in disease detection.
- New drug discoveries are due to understanding chemicals in the human body
- Personalised medicine is based on metabolomics data, which enables us to predict bespoke treatment for individuals
Challenges and limitations in metabolomics
- The complexity of data; there are many databases and evolving techniques of analysis. Therefore, the integration and cooperation of databases must be done.7
- Accuracy of metabolite identification. Many detected metabolites are still unknown metabolites, for they do not exist in any databases. Advancing the technologies for metabolic profiling is the key.
- Integration with other omics data, including genomics, transcriptomics, and proteomics. This will provide a comprehensive understanding of biological systems, which is still challenging in terms of preparation and data analysis techniques.
- The costs of the procedures and health system must be developed to be comprehensive in routine healthcare to create equity and coverage.
Summary
Metabolomics is one of the emerging health technologies in our world. Challenges to utilisation in routine healthcare still exist; however, its potential to improve outcomes of healthcare and individual health is promising. Keeping up-to-date on health technologies will raise your awareness of the world's relentless improvement and give you great opportunities.
References
- Clish CB. Metabolomics: an emerging but powerful tool for precision medicine. Cold Spring Harb Mol Case Stud [Internet]. 2015 Oct [cited 2023 Jul 14];1(1):a000588. Available from: http://molecularcasestudies.cshlp.org/lookup/doi/10.1101/mcs.a000588
- Alseekh S, Fernie AR. Metabolomics 20 years on: what have we learned and what hurdles remain? Plant J [Internet]. 2018 Jun [cited 2023 Jul 20];94(6):933–42. Available from: https://onlinelibrary.wiley.com/doi/10.1111/tpj.13950
- Link H, Fuhrer T, Gerosa L, Zamboni N, Sauer U. Real-time metabolome profiling of the metabolic switch between starvation and growth. Nat Methods [Internet]. 2015 Nov [cited 2023 Oct 29];12(11):1091–7. Available from: https://www.nature.com/articles/nmeth.3584
- Alseekh S, Aharoni A, Brotman Y, Contrepois K, D’Auria J, Ewald J, et al. Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices. Nat Methods [Internet]. 2021 Jul [cited 2023 Jul 14];18(7):747–56. Available from: https://www.nature.com/articles/s41592-021-01197-1
- Nguyen TTM, An YJ, Cha JW, Ko YJ, Lee H, Chung CH, et al. Real-time in-organism nmr metabolomics reveals different roles of amp-activated protein kinase catalytic subunits. Anal Chem [Internet]. 2020 Jun 2 [cited 2023 Jul 20];92(11):7382–7. Available from: https://pubs.acs.org/doi/10.1021/acs.analchem.9b05670
- Riekeberg E, Powers R. New frontiers in metabolomics: from measurement to insight. F1000Res [Internet]. 2017 Jul 19 [cited 2023 Jul 20];6:1148. Available from: https://f1000research.com/articles/6-1148/v1
- Johnson, Caroline H., and Frank J. Gonzalez. ‘Challenges and Opportunities of Metabolomics’. Journal of Cellular Physiology, vol. 227, no. 8, Aug. 2012, pp. 2975–81. Available from: https://doi.org/10.1002/jcp.24002.