The Role of Metabolomics in Precision Medicine

Precision medicine is a prevention and treatment strategy tailored to an individual. Given the complexity of genetic, epigenetic, physiological, and environmental variabilities amongst individuals a one-size-fits-all approach to medicine is no longer viable. Therefore, an individual’s biochemical or metabolic characterization using “omics’ technology is key to precisely defining phenotypes.

Precision Medicine Concept

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Metabolomics is a technology that is a powerful tool in the global and comprehensive assessment of an individual's biochemical or metabolic profile. Metabolic profiles can map the global effects of drugs on metabolism and also identify the mechanism of action of the drug on individuals. A baseline metabolic profile as a first line of treatment could inform about disease heterogeneity and treatment outcomes.

Metabolomics brings us closer to expressing phenotype, enabling us to look at genotype-phenotype, as well as genotype-envirotype relationships. Small molecules or metabolites have been utilized to diagnose disease and impact clinical care for decades. For example, use of blood glucose test strips for diabetes or measuring phenylalanine in newborns to screen for phenylketonuria.

Metabolomic analysis

The fundamental goal of metabolome analysis is accurate identification and quantification of all the metabolites in a cellular system. Metabolomic studies follow a typical workflow involving three major steps.

First, sample separation which simplifies a complex mixture followed by detection using methods such as gas chromatography (GC) or high-pressure liquid chromatography (HPLC). The metabolites in the mixture are then quantified using advanced detection methods such as mass spectrometry (MS) or nuclear magnetic resonance (NMR). Finally, data is analyzed by statistical methods such as XCMS.

Applications of metabolomics

The total number of small molecules which constitute the human metabolome is around 40,000. This includes metabolites associated with endogenous enzymatic activities, those derived from food and medications, the microbiota as well as the environment. Metabolites differ not only in size, distribution, and abundance but also in their physicochemical characteristics.

The role of metabolomics in modern precision medicine is an important one, as it offers comprehensive coverage of biological and metabolic pathways creating a “metabolic fingerprint” of a sample. Metabolomics uses a non-selective approach of assessing metabolites which allows simultaneous coverage and accurate quantification of a wide range of known biomarkers including markers for cardiovascular disease, diabetes mellitus, neurodegenerative disorders, and cancer, etc.

Early diagnosis and characterization of disease phenotypes

Metabolite patterns can be utilized to distinguish between two subjects thus enabling detailed metabolic characterization. This could not only identify the metabolic pathways involved in the disease phenotype but could also unravel new and unknown metabolic pathophysiological pathways.

Metabolic profiling can help in the diagnosis of tumor types. In breast cancer specimens there are over 30 endogenous metabolites including increased phosphocholine, low glycerophosphocholine, and low glucose which can be indicative of disease prognosis. Micrometastases could be predicted in breast cancer patients, with increased plasma glucose, proline, lysine, phenylalanine, N-acetylcysteine, and decreased lipid levels. Similarly, metabolic signatures for ovarian cancer, lung cancer, endometrial cancer, and colorectal cancer have been mapped. Thus, metabolomics can be used to predict metastasis, disease progression, and overall survival in cancer patients.

Predicting drug effectiveness and/or toxicity or pharmacometabolomics

This is a branch of metabolomics related to the effect of drugs on a biological system. Pharmacometabolomics is key to the future of precision medicine. Metabolite levels can predict the rate of response to a drug and can also be used to distinguish candidates who will respond to a particular drug treatment from the non-responders.

For example, targeted metabolomics was applied in evaluating metabolic signatures of responders and non-responders to L-carnitine treatment for life-threatening sepsis. Individuals with high levels of 3-hydroxybutyrate, acetoacetate, and 3-hydroxyvaleric acid before treatment with L-carnitine had a favorable drug response and improved survival. Such pharmacometabolomic findings help in the metabolic phenotyping of L-carnitine responders and identify alternate care for those identified as non-responders.

Predicting drug toxicity

Metabolomics can also assist in predicting drug toxicity. For example, treatment of atopic dermatitis in infants consists of topical steroids or steroid-free topical calcineurin inhibitors (TCI), both associated with serious complications. Metabolomics helps in assessing clinical data by functional interpretation and predicting toxicity and systemic reactions of long-term drug therapy thus preventing adverse drug reactions.

Drug development

Clinical trials are a laborious, time-consuming, and expensive endeavor. Metabolomics to predict drug response and toxicity could be beneficial in effective drug development. Metabolic profiles provide insights into the variation of response to antipsychotics, statins, antidepressants, antihypertensives, antiplatelet therapies, and the development of side effects to treatment.

Knowing which patients tolerate a drug provides clinicians with a huge advantage in ensuring the success of drugs as well as providing patients with the best possible outcome.

Pediatrics

Pediatric metabolomics plays an important role in precision medicine. Metabolic profiling is useful in the diagnosis of inborn errors in metabolism such as putative gain-of-function mutations in genes encoding metabolic enzymes such as isocitrate dehydrogenase (IDH).

Mutated IDH1 and IDH2 proteins catalyze a reaction resulting in the formation of 2-hydroxyglutarate (2-HG) which inhibits α-ketoglutarate-dependent dioxygenases which regulate the epigenetic state of cells. IDH inhibitors have shown favorable outcomes in solid tumors with IDH mutations, including cholangiocarcinomas and low-grade gliomas.

Conclusion

The role of metabolomics in precision medicine is to tailor therapies for each individual by delivering more effective drug treatments while avoiding adverse drug reactions. Metabolomics offers not only a better understanding of the molecular determinants of disease but also helps in the development of new biomarkers for the diagnosis, prognosis, and treatment of disease.

Metabolomics plays a role in unraveling novel drug targets for therapies. Metabolomics reduces the cost of toxicological screens and speeds up the drug development process. We are at the cutting edge of therapy where metabolomics is beginning to revolutionize precision medicine by developing personalized phenotyping and individualized drug response monitoring.

It is just a matter of time when metabolomics technology will be employed in routine clinical practice to not only help clinicians but also to empower patients, through a deeper understanding of disease mechanisms and therapy.

Sources:

  • Puchades-Carrasco, L. and Pineda- Lucena, A. (2017). Metabolomics Applications in Precision Medicine: An Oncological Perspective. Current Topics in Medicinal Chemistry, 17(24).
  • Wishart, D.S. (2016). Emerging applications of metabolomics in drug discovery and precision medicine. Nature Reviews Drug Discovery, [online] 15(7), pp.473–484.
  • Yang, Q., Zhang, A., Miao, J., Sun, H., Han, Y., Yan, G., Wu, F. and Wang, X. (2019). Metabolomics biotechnology, applications, and future trends: a systematic review. RSC Advances, [online] 9(64), pp.37245–37257.
  • Ashrafian, H., Sounderajah, V., Glen, R., Ebbels, T., Blaise, B.J., Kalra, D., Kultima, K., Spjuth, O., Tenori, L., Salek, R., Kale, N., Haug, K., Schober, D., Rocca-Serra, P., O’Donovan, C., Steinbeck, C., Cano, I., de Atauri, P. and Cascante, M. (2020).
  • Metabolomics - the stethoscope for the 21st century. Medical Principles and Practice.
  • Holmes, E., Wijeyesekera, A., Taylor-Robinson, S.D. and Nicholson, J.K. (2015). The promise of metabolic phenotyping in gastroenterology and hepatology. Nature Reviews Gastroenterology & Hepatology, [online] 12(8), pp.458–471.
  • Wishart, D.S. (2016). Emerging applications of metabolomics in drug discovery and precision medicine. Nature Reviews Drug Discovery, [online] 15(7), pp.473–484.

Further Reading

Last Updated: Nov 26, 2021

Dr. Poornima Balaji

Written by

Dr. Poornima Balaji

Poonam is passionate about all things science and medicine. She has over 20 years of experience in research in cardiovascular physiology, biochemistry, and molecular biology. Poonam has worked as an independent scientist both in the United States and in Australia and has several publications in high-impact journals. (11 publications with ~700 citations; h index of 11).

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