Chrono-Nutrition: Circadian Rhythm and Personalized Nutrition

Abstract

The human circadian system has a period of approximately 24 h and studies on the consequences of "chornodisruption" have greatly expanded. Lifestyle and environmental factors of modern societies (i.e., artificial lighting, jetlag, shift work, and around-the-clock access to energy-dense food) can induce disruptions of the circadian system and thereby adversely affect individual health. Growing evidence demonstrates a complex reciprocal relationship between metabolism and the circadian system, in which perturbations in one system affect the other one. From a nutritional genomics perspective, genetic variants in clock genes can both influence metabolic health and modify the individual response to diet. Moreover, an interplay between the circadian rhythm, gut microbiome, and epigenome has been demonstrated, with the diet in turn able to modulate this complex link suggesting a remarkable plasticity of the underlying mechanisms. In this view, the study of the impact of the timing of eating by matching elements from nutritional research with chrono-biology, that is, chrono-nutrition, could have significant implications for personalized nutrition in terms of reducing the prevalence and burden of chronic diseases. This review provides an overview of the current evidence on the interactions between the circadian system and nutrition, highlighting how this link could in turn influence the epigenome and microbiome. In addition, possible nutritional strategies to manage circadian-aligned feeding are suggested.

Keywords: chronodisruption; clock genes; epigenetics; gene–diet interaction; gut microbiome; nutrigenetics; personalized nutrition.

Figure 1

Molecular mechanisms controlling the circadian rhythm. CLOCK and BMAL1 regulate the expression of numerous genes including Per family (Per1-3), Cry family (Cry1-2), nuclear receptor family (Rev-erbα and Rorα), and many downstream target genes known as clock-controlled genes (Ccg). CRY and PER proteins translocate to the nucleus to form a negative-feedback repressor complex of CLOCK/BMAL1 transcriptional activity. Another feedback loop, driven by CLOCK:BMAL1, involves Rev-erbα and Rorα to regulate Bmal1 transcription. At a post-transcriptional level, SCF (Skp1-Cullin-F-box protein) E3 ubiquitin ligase complexes regulate PER and CRY proteins’ stability by recognizing specific targets and directing their polyubiquitination. Finally, their degradation is regulated by the 26S proteasome complex.

Figure 2

Panel (A) From a nutritional genomics perspective, summary of the complex diet–biological rhythm-omics interplay related to health outcomes. Personalized nutrition considering an individual’s genome and epigenome combined with chrono-nutrition could contribute to the fight against non-communicable diseases. Panel (B) Diet, chronotype, and several environmental disruptions of modern societies can impact the integration of circadian-triggering metabolic alterations and lead the development of chronic disease mitigation.