A web of metabolic interactions allows us to describe the cell: the genome (the complete set of genes or genetic material present in a cell or organism), transcripts (RNA molecules of a cell) and lastly, proteins. In the cell everything is ready to let metabolic processes begin, both the easiest and the most difficult ones, the common ones and the cell-type specific ones.
The metabolites (both the final ones and the pathways’ intermediate ones) provide the cell an unique fingerprint, eloquent hint of the processes that happened.
In 1940 Roger Wlliams was the first one to introduce the concept of “metabolic fingerprint” like a characteristic trait of every individual: the term “Metabolomics” was then introduced to describe the scientific discipline that deals with the identification of metabolites that characterize the cellular biological processes.
Metabolomics deals with the study of these marks, the systematic study of “biochemical footprints” left by metabolic processes and represented by metabolites themselves. All the metabolites, the small molecules found in a cell (or, comprehensively, in a tissue, organ or organism), make up the metabolome.
We’ve talked about footprints and marks, but we can compare metabolomics to a snapshot of the cell that tells us what it is doing and in which stage of cellular cycle it is, if it is dealing with a stressful situation or if it is easily performing its physiological role.
Welcome in -omics sciences’ world and in their potentialities!
In -omic sciences’ group, metabolomics is at the base of a pyramid whose top has genic information analysis, genomics, then genic expression analysis or transcriptomics and lastly the analysis of cells’ proteins, proteomics.
A science older than what we could think
Don’t let us be fooled by -omics suffix: metabolomics is as old as medicine! Since Hippocrates and his humors’ medicine, the intuitive analysis of body fluids was used as diagnostic tool; the same happened in the Middle Ages, when the ancestor of modern urine analysis allowed the understanding of a patient’s health status (tasting urines to know if they were sweet was a primitive diabetes diagnosis!).
The metabolic profile concept dates back to ‘40s and refers to an individual’s characteristic metabolic pattern found in easily analysable body fluids like urine and saliva. Roger Williams introduced that concept while studying schizophrenia using chromatography. It was the beginning of metabolomics, even if there were no means for a quantitative analysis of metabolites. The transition from qualitative to quantitative took place in the ‘70s thanks to the combination of gas chromatography (a technique based on the breakdown of a mixture’s components) and mass spectrometry (analytical technique which separates ions with the same charge and different mass) by Horning, Pauling and Robinson.
In the same years, the use Nuclear Magnetic Resonance (investigation technique which bases on the use of a magnetic field) for spectroscopic analysis (spectroscopy is a science which measures light intensity at different wavelengths) was applied to the study of metabolites in biological samples.
In 2007 the Human Metabolome Project, driven by a Canadian equipe, completed a first draft of human metabolome.
The Human Metabolome Database has more than 40.000 metabolites.
METABOLOMICS’ CLINICAL APPLICATIONS
In National Institutes of Health (NIH) opinion, Precision Medicine is “an emerging approach for treatment and prevention of diseases that considers the individual variability of genes, environment and lifestyle of every person”.
Precision Medicine is juxtaposed to the current “4P medicine”: predictive, preventive, personalized and participatory.
This approach should allow doctors and researchers to predict more accurately which treatment and/or prevention for a specific disease will work for a certain group of patients and/or people. This will permit the diagnosis of specific causal factors and the specific and effective treatment of deep disease’s causes.
The applications of metabolomics regard different fields, more or less linked to clinical practice.
Metabolomic analysis allows us not only the identification of biochemical changes (even the early ones) associated to the use of drugs or to the exposure to pollutants, but also the ones that indicate still asymptomatic pathological situations. The onset of a neoplastic disease, even in early stages of clinical latency, is associated with metabolome alterations that could be used for early diagnosis. The same is valid for dyslipidemias and cardiovascular diseases, in the phases that precede the symptomatology evidence, not to talk about neurodegenerative diseases like Alzheimer, Parkinson and SLA, in which the diagnosis is often late.
The field in which metabolomics had the biggest success and utility is the one of prevention and prognosis of multifactorial diseases, in which the metabolic description of a specific phenotype is required.
Differently from hereditary genetic diseases, for which the availability of a limited amount of biomarkers could be sufficient for the diagnosis and prognosis of a pathology, in multifactorial diseases like obesity, the aim is to identify a metabolic signature of hundreds of metabolites.
In this context, Metabolomics availability has a vital importance for the comprehension of the role of each metabolite in biological processes.
NUTRIMETABOLOMICS: the future of personalized medicine
In conclusion and considering the new personalized approach of medicine, today we can also talk about nutrimetabolomics. The basic concept consists in the possibility of identifying, at personalized level, our metabolic map.
Understanding our metabolism considering every single metabolite so that we can establish a correct nourishment for the demand of every phenotype.
An example: the analysis of our metabolic profile alerts us about a particular predisposition for the onset of metabolic syndrome. Well, knowing this and acting in advance we can take care of our diet and our lifestyle in a personalized manner so that we can change and qualify our metabolism.
- Rivista Società Italiana di Medicina Generale N.6 VOL.25 2018
- Piero Cappelletti Riv Ital Med Lab (2016); Medicina di Precisione e Medicina di Laboratorio Precision Medicine and Laboratory Medicine
- Hollywood K, Brison DR, Goodacre R (September 2006). “Metabolomics: current technologies and future trends”. Proteomics. 6 (17): 4716–23.
- Cirulli ET, Guo L, Leon Swisher C et al. Profound perturbation of the metabolome in obesity associates with health risk. Cell Metab. doi:10.1016/j.cmet.2018.09.022 (2018)