BACKGROUND: Subliminal oxidative stress and systemic inflammation, putatively mediated/modulated by long-term nutrimetabolic imbalance, are known pathophysiologic mechanisms in chronic disease development. Their early detection may enable timely intervention to prevent onset, favorably alter course or mitigate outcome of chronic disorders. Contemporary healthcare framed in a biomedical reductionist health-disease dualism so far has largely disregarded predisease and malnutrition phenotypes, perhaps by reason of paradigmatic reluctance and technological limitations. Primarily focused on clinical disease, conventional circulating biomarkers unable to capture the complexity of multiple actors, targets and levels of biological organization, thus, may fail to yield actionable results.
OBJECTIVE: This work aims to evaluate the strengths and weaknesses of the nutritional phenotype‟s post-genomic subset (nutritional transcriptome, proteome, and metabolome) in illuminating molecular signatures indicating early homeostatic perturbations of chronic disease. The term “nutritional phenotype” denotes “a defined and integrated set of genetic, proteomic, metabolomic, functional, and behavioral factors that, when measured, form the basis for assessment of human nutritional status. [It] integrates the effects of diet on disease/wellness and is the quantitative indication of the paths by which genes and environment exert their effects on health (Zeisel et al, J Nutr 2005 Jul, 135(7):1613-6).”
METHODOLOGY: A PUBMED literature survey has been carried out to retrieve published material (reviews and original research) between 1999 and 2010 linking post-genomic technologies to the early detection of molecular redox and inflammation states.
FINDINGS: In general, post-genomics provides insight into biopathologic mechanisms and regulatory networks; challenges may largely arise from experiments (eg, study design, (pre-)analytics, tissue availability, protocols), biology (eg, intersubject variability, marginal dietary ad-hoc effects) and technology (eg, innate limitations, low dietary signal-to-noise ratio, inter-assay/platform/laboratory variability, standards, systems, infrastructure, laboratory equipment). Beyond this, each technology naturally features specific pros and cons (transcriptomics: eg, illuminating functional relationships vs. limited capacity to reliably predict the ultimate phenotype; proteomics: eg, identifying/quantifying protein abundance, function, activity, interactions etc. vs. complexity due to protein diversity, dynamics, localization etc.; metabolomics: eg, assessing net metabolic effects vs. comprehending genome-microbiome crosstalk). In a nutshell, although nutrigenomic profiling studies targeting aberrant redox/inflammation states are scarce, preliminary evidence based on various biofluids, cell types, model systems and disorders furnish proof of its capacity and enormous potential in deciphering unique molecular signatures.
CONCLUSION: Well-designed (integrative) nutrigenomic profiling studies plus challenge tests may enable assessment of homeostatic robustness as well as detection of early onset and magnitude of physiologic derangements in redox and inflammation related networks. Further studies employing nutritional phenotype (subsets) are warranted to early assess nutritional, metabolic and health status of yet asymptomatic individuals as part of a comprehensive prevention, risk assessment and health promotion program.