Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

METABOLOMICS: DEFINITIONS, STATE-OF-THE-ART AND REPRESENTATIVE APPLICATIONS.Metabolomics is an emerging and promising omics approach used to understand biological mechanisms. By untargeted and targeted metabolomics analyses, metabolites are determined in biological samples (fluids, cells, tissues, etc.) by comparison of control groups with altered groups, undergoing different therapies, submitted to differing stress levels, dietary modulation, or promoted by a disease, or specific condition, etc., using sophisticated analytical techniques, and advanced data treatment and statistical analyses. In this review, the concepts involved in metabolomics studies were presented, describing in details all steps involved in the metabolomics workflow, for untargeted and targeted strategies. Finally, the potential of metabolomics is illustrated by applications in representative areas: clinical, environmental, food and nutrition, forensic toxicology, microbiology, parasitology, plants, and sports. Relevant reviews were compiled to characterize each of these areas, and a corresponding application of untargeted and targeted metabolomics were described.Keywords: metabolomics; untargeted metabolomics; targeted metabolomics; metabolomics workflow. INTRODUÇÃOAs ciências ômicas buscam o entendimento do funcionamento celular dos organismos e suas alterações biológicas. Fazem parte deste conjunto de ciências, a genômica (estudo da alteração dos genes), a transcriptômica (estudo das alterações dos transcritos), a proteômica (estudo das alterações das proteínas), e a metabolômica (estudo das alterações dos metabólitos). Metabólitos são produtos intermediários ou finais do metabolismo em uma amostra biológica.1 O conjunto de todos os metabólitos de baixa massa molecular (até 1500 Da), presentes ou alterados em um sistema biológico, é chamado de metaboloma (do inglês, metabolome).2 A pesquisa relacionada a metabólitos vem sendo desenvolvida há décadas, mas em 1999, Nicholson et al. definiram a metabonômica (do inglês, metabonomics), como sendo a medida quantitativa da resposta metabólica de um sistema biológico após estímulos fisiopatológicos ou modificações genéticas.3 Já o termo metabolômica (do inglês, metabolomics) foi introduzido em 2001, por Oliver Fiehn, como sendo a análise abrangente e quantitativa do metaboloma de um sistema biológico. 4 Além disso, a literatura nos apresenta outras denominações envolvendo esse campo da ciência, tais como: perfil metabólico (do inglês, metabolic profiling), descrito como sendo a análise de metabólitos previamente selecionados de rotas bioquímicas específicas, 5 a impressão digital metabólica (do inglês, metabolic fingerprinting), que é definida como sendo "uma classificação de amostras de acordo com sua origem ou sua relevância biológica", 3 e, por último, análise footprinting (ainda sem tradução para o português), para se referir aos metabólitos excretados por uma célula em condições controladas. Observa-se, portanto, uma divergência em relação às terminologias aplicadas às análises metabolômic...

This review article compiles in a critical manner literature publications regarding seven neglected diseases (ND) prioritized in Brazil (Chagas disease, dengue, leishmaniasis, leprosy, malaria, schistosomiasis, and tuberculosis) under the perspective of metabolomics. Both strategies, targeted and untargeted metabolomics, were considered in the compilation. The majority of studies focused on biomarker discovery for diagnostic purposes, and on the search of novel or alternative therapies against the ND under consideration, although temporal progression of the infection at metabolic level was also addressed. Tuberculosis, followed by schistosomiasis, malaria and leishmaniasis are the diseases that received larger attention in terms of number of publications. Dengue and leprosy were the least studied and Chagas disease received intermediate attention. NMR and HPLC-MS technologies continue to predominate among the analytical platforms of choice in the metabolomic studies of ND. A plethora of metabolites were identified in the compiled studies, with expressive predominancy of amino acids, organic acids, carbohydrates, nucleosides, lipids, fatty acids, and derivatives.

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