Allostasis and Resilience of the Human Individual Metabolic Phenotype

The urine metabotype of 12 individuals was followed over a period of 8-10 years, which provided the longest longitudinal study of metabolic phenotypes to date. More than 2000 NMR metabolic profiles were analyzed. The majority of subjects have a stable metabotype. Subjects who were exposed to important pathophysiological stressful conditions had a significant metabotype drift. When the stress conditions ceased, the original metabotypes were regained, while an irreversible stressful condition resulted in a permanent metabotype change. These results suggest that each individual occupies a well-defined region in the broad metabolic space, within which a limited degree of allostasis is permitted. The insurgence of significant stressful conditions causes a shift of the metabotype to another distinct region. The spontaneous return to the original metabolic region when the stressful conditions are removed suggests that the original metabotype has some degree of resilience. In this picture, precision medicine should aim at reinforcing the patient's metabolic resilience, that is, his or her ability to revert to his or her specific metabotype rather than to a generic healthy one.