Potential mechanisms of precision nutrition-based interventions for managing obesity

Precision nutrition (PN) considers multiple individual-level and environmental characteristics or variables, in order to better inform dietary strategies and interventions for optimizing health, including managing obesity and metabolic disorders. Here, we review the evidence on potential mechanisms – including ones to identify those most likely to respond – that can be leveraged in the development of PN interventions addressing obesity. We conducted a review of the literature and included laboratory, animal, and human studies evaluating biochemical and genetic data, completed and ongoing clinical trials, and public programs in this review. Our analysis describes the potential mechanisms related to six domains including genetic predisposition; circadian rhythms; physical activity and sedentary behavior; metabolomics; the gut microbiome, and behavioral and socioeconomic characteristics; i.e. the factors that can be leveraged to design PN-based interventions to prevent and treat obesity-related outcomes such as weight loss or metabolic health as laid out by the NIH 2030 Strategic Plan for Nutrition Research. For example, single nucleotide polymorphisms (SNPs) can modify responses to certain dietary interventions, and epigenetic modulation of obesity risk via physical activity patterns and macronutrient intake have also been demonstrated. Additionally, we identified limitations including questions of equitable implementation across a limited number of clinical trials. These include the limited ability of current PN interventions to address systemic influences such as supply chains and food distribution, healthcare systems, racial or cultural inequities, and the economic disparities particularly when designing and implementing PN interventions in low- and middle-income communities. PN has the potential to treat obesity by addressing inter-individual variation, as opposed to a "one-size fits all" standardized intervention, though there is limited clinical trial evidence to date. Optimizing dietary strategies and interventions at the individual level through genetic and microbiome assessment, lifestyle pattern analysis, and phenotyping may help advance our ability to modulate and/or manage individualized physiological factors involved in obesity.