It is now widely known, lifestyle choices are pivotal for a person’s health and life quality, and it is estimated that at least 40% and up to 95% of chronic illnesses can be traced back to lifestyle risk factors (e.g. smoking, lack of physical activity and dietary habits) [1, 2]. Moreover, a positive correlation between the adoption of healthy lifestyle choices and a reduced risk of mortality as well as postponing or even avoiding many types of chronic illnesses such as cancer, cardiovascular diseases and metabolic syndrome, has been demonstrated [1, 3-8]. Insulin resistance, abnormal lipid metabolism, diabetes and hypertension are risk factors highly correlated with obesity [9-11], while smoking is known to cause several cancers, especially of the lung and upper airways [12, 13]. In contrast, regular physical activities as well as healthy eating habits such as the Mediterranean diet [14] have already shown to reduce the risk of several chronic conditions such as cardiovascular disease [15, 16], to play a protective role in cancer prevention [17], to promote longevity [18] and to decrease the risk of developing metabolic syndrome and type 2 diabetes [19]. Observational studies suggest that lifestyle changes, mainly dietary [20], can improve the immune system and reduce the risk of recurrence of certain types of cancers, such as ovarian cancer [21]. Therefore, fast and efficient monitoring of biomarkers reflecting individual lifestyle patterns could play a preventive role in the development of chronic disorders.
The investigation of metabolic response to environmental exposures is an emerging field of research in toxicology [22, 23]. The so-called exposome includes not only exogenous exposure to the environment, diet or lifestyle factors but also to biological processes reflecting internal responses to exposure [24-26]. For example, a chronic low-dose exposure to mycotoxins, which are frequently detected as natural contaminants in foods, have already been associated with the onset of various diseases. The analysis of mycotoxins as biomarkers for exposure to contaminated food was successfully performed using plasma, serum, urine and milk samples [27, 28]. The origin of many metabolites, which are either endogenously produced, originate from the gut microbiome, or come from the environment via nutrition or smoking is already being investigated in great detail [29]. In particular, serum metabolomics has successfully revealed several biomarkers which have improved our understanding of disease mechanisms and which are being used in clinical settings for the diagnosis of diseases as well as in the monitoring of therapeutic outcomes [30].
A comprehensive analysis of endogenous processes related to the uptake and individual metabolism of xenobiotics requires sensitive analytical techniques in addition to non-invasive and fast sampling methods, allowing short interval sampling and therefore enabling kinetic time-course measurements in humans [31, 32]. The analysis of sweat from the fingertips fulfils these requirements and supports compliance of test subjects. Over decades, fingerprints have been used to identify individuals and more recently play an important role in lifestyle monitoring via imaging mass spectrometry [33]. Exogenous compounds found in bug sprays and sunscreens as well as food oils, alcohols and citrus fruits were detected in fingerprints, offering relevant chemical information about the tested person [34]. Moreover, fingerprints are used to detect illicit drugs and their metabolites [35, 36]. In contrast to the investigation of fingerprints, the analysis of sweat has been successfully proven in diagnostic medicine to enable the monitoring of individual metabolic and health states [37-39]. Sweat is mainly composed of water (99%), but includes also numerous substances such as electrolytes, lactate, pyruvate, urea, amino acids, proteins, peptides, fatty acids, hormones and xenobiotics (e.g. cosmetics, medications and drugs including ethanol) [40]. Antibodies and cytokines detected in sweat may serve as potential biomarkers for diseases [41] and, as already demonstrated, for disease states in cystic fibrosis [42] and active tuberculosis [43]. Moreover, cortisol has been successfully quantified in human eccrine sweat, demonstrating the potential of finger sweat analysis in regard to monitor endogenous processes related to stress [44].
Only recently, we successfully demonstrated kinetic time-course measurements of metabolic activities in humans, indicating that finger sweat analyses may become a valuable tool for precision medicine [32]. In contrast to other minimally invasive approaches [45, 46], the presented non-invasive metabolomics assay works quickly and easily while offering tremendous investigative power. We have termed it “metabo-tip”. Indeed, the ingestion of many bioactive compounds contained in food may become detectable via metabo-tip within minutes after consumption. Applying mathematical modelling strategies, it was possible to overcome critical normalization challenges and to obtain quantitative measures for individual metabolic properties [32]. In this project, we investigated metabo-tip in regards to monitoring lifestyle parameters such as the presence of endogenous and exogenous bioactive compounds or exposure to toxins contained in foods or beverages. These parameters could be described by time-dependent metabolic patterns detected in sweat from the fingertip. The observation of metabolic diurnal rhythms and distinct individual responses to potentially adverse exposure promises successful future applications of metabo-tip analysis not only in the general assessment of individual lifestyle-parameters but also in predictive preventive personalised medicine (PPPM).