The predictive power of an unhealthy metabolome

Credit: Jennie Vallis/Springer Nature Limited

New research has identified the changes that occur to the human metabolome, which represents the collection of all the small metabolites produced during metabolism, following an increase in body weight. Furthermore, the authors were able to use these data to predict whether an individual would go on to develop the metabolic syndrome.

In their study, the authors used whole-genome sequencing and untargeted metabolomics to assess the diversity of the metabolome in human obesity in >2,000 individuals from the TwinsUK cohort, which had an average follow-up time of 13 years. “We were taken by surprise by the large-scale perturbation of the metabolome following weight gain — many pathways and systems were altered with increasing body weight,” explains co-corresponding author Amalio Telenti.

Furthermore, individuals who had the same BMI, but different metabolome signatures, had slightly different genetic signatures. “Specifically, people with an unhealthy metabolome but healthy BMI had a lower genetic risk of obesity than people who had a healthy metabolome but unhealthy BMI,” adds Elizabeth Cirulli, the other corresponding author on the study.

Therefore, the data suggest that how an individual’s metabolome reacts to excess weight or a positive calorie intake, and not the physical measurement of obesity by BMI, is what is important for overall health. In other words, some people are genetically predisposed to have a BMI in the overweight or obese categories, but if these individuals lead healthy lifestyles they can have healthy metabolomes and benefit from good overall health. By contrast, people who are genetically predisposed to have a BMI in the normal-weight category that lead unhealthy lifestyles can suffer from negative health outcomes.

“It is really exciting that we are able to use a blood test to characterize the overall health of a person in a more robust way than we can do by measuring BMI alone,” concludes Cirulli. “I think future studies using metabolites to characterize different aspects of a person’s health will lead to breakthroughs in how we can assess a person’s risk of developing different diseases.”