Metabolic phenotyping of tear fluid as a prognostic tool for personalised medicine exemplified by T2DM patients

Background/AimsOne goal of predictive, preventive, and personalised medicine is to improve the prediction and diagnosis of diseases, as well as to monitor therapeutic efficacy and to tailor individualised treatments with as little side effects as possible. New methodological developments should preferably rely on non-invasively sampled biofluids like sweat and tears in order to provide optimal compliance. Here we have thus investigated the metabolic composition of human tears in comparison to finger sweat and evaluated whether tear analyses may provide insight into ocular and systemic disease mechanisms.MethodsIn addition to finger sweat, tear fluid was sampled from 20 healthy volunteers using commercially available Schirmer strips. Tear fluid extraction and analysis using high-resolution mass spectrometry hyphenated with liquid chromatography was performed with optimized methods each for metabolites and eicosanoids. As second approach, we performed a clinical pilot study with 8 diabetic patients and compared them to 19 healthy subjects.ResultsTear fluid was found to be a rich source for metabolic phenotyping. Remarkably, several molecules previously identified by us in sweat were found significantly enriched in tear fluid, including creatine or taurine. Furthermore, other metabolites such as kahweol and various eicosanoids were exclusively detectable in tears, demonstrating the orthogonal power for biofluid analysis in order to gain information on individual health states. The clinical pilot study revealed that many endogenous metabolites that have previously been linked to type 2 diabetes such as carnitine, tyrosine, uric acid and valine were indeed found significantly up-regulated in tears of diabetic patients. Nicotinic acid and taurine were elevated in the diabetic cohort as well and may represent new biomarkers for diabetes specifically identified in tear fluid. Additionally, systemic medications like metformin, bisoprolol, and gabapentin, were readily detectable in tears of patients. These findings highlight the potential diagnostic and prognostic power of tear fluid analyses, in addition to the promising methodological support for pharmacokinetic studies and patient compliance control.ConclusionsTear fluid analysis may support the development of clinical applications in the context of predictive, preventive, and personalised medicine as it reveals rich molecular information in a non-invasive way.

All around suboptimal health — a joint position paper of the Suboptimal Health Study Consortium and European Association for Predictive, Preventive and Personalised Medicine

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person.This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions: Stress overload associated pathologies Male and female health Planned pregnancies Periodontal health Eye disorders Inflammatory disorders, wound healing and pain management with associated complications Metabolic disorders and suboptimal body weight Cardiovascular pathologies Cancers Stroke, particularly of unknown aetiology and in young individuals Sleep medicine Sports medicine Improved individual outcomes under pandemic conditions such as COVID-19.

Metabo-tip: a metabolomics platform for lifestyle monitoring supporting the development of novel strategies in predictive, preventive and personalised medicine

Background/aims Exposure to bioactive compounds from nutrition, pharmaceuticals, environmental contaminants or other lifestyle habits may affect the human organism. To gain insight into the effects of these influences, as well as the fundamental biochemical mechanisms behind them, individual molecular profiling seems to be a promising tool and may support the further development of predictive, preventive and personalised medicine. Methods We developed an assay, called metabo-tip for the analysis of sweat, collected from fingertips, using mass spectrometry—by far the most comprehensive and sensitive method for such analyses. To evaluate this assay, we exposed volunteers to various xenobiotics using standardised protocols and investigated their metabolic response. Results As early as 15 min after the consumption of a cup of coffee, 50 g of dark chocolate or a serving of citrus fruits, significant changes in the sweat composition of the fingertips were observed, providing relevant information in regard to the ingested substances. This included not only health-promoting bioactive compounds but also potential hazardous substances. Furthermore, the identification of metabolites from orally ingested medications such as metamizole indicated the applicability of this assay to observe specific enzymatic processes in a personalised fashion. Remarkably, we found that the sweat composition fluctuated in a diurnal rhythm, supporting the hypothesis that the composition of sweat can be influenced by endogenous metabolic activities. This was further corroborated by the finding that histamine was significantly increased in the metabo-tip assay in individuals with allergic reactions. Conclusion Metabo-tip analysis may have a large number of practical applications due to its analytical power, non-invasive character and the potential of frequent sampling, especially regarding the individualised monitoring of specific lifestyle and influencing factors. The extraordinarily rich individualised metabolomics data provided by metabo-tip offer direct access to individual metabolic activities and will thus support predictive preventive personalised medicine.