The Effects of Chrononutrition on Circadian Rhythm, Gut Microbiota Diversity and Cardiometabolic Outcomes in Type 2 Diabetes Mellitus: A Systematic Review Protocol

Type 2 diabetes mellitus (T2DM) is a major public health challenge and is increasingly associated with an imbalance in gut microbiota composition. Recent advances in chrononutrition, which focus on synchronising meal timing with the body’s internal biological clock (circadian rhythm), have gained attention as a potential modifiable factor of host metabolism and gut microbial diversity. Nonetheless, whether chrononutrition, circadian rhythm biomarkers, gut microbiota and cardiometabolic outcomes are associated, specifically in T2DM, remains fragmented. Therefore, we aim to conduct a systematic review of studies that evaluated the effects of chrononutrition-related dietary patterns on circadian rhythm biomarkers, gut microbial diversity and cardiometabolic outcomes in T2DM. We have structured the protocol following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines. Search of relevant studies will be executed using four databases, such as PubMed, EMBASE, Web of Science and the Cochrane Library, which involve records from their respective inception up to February 2026. The eligibility criteria for the population are adults with T2DM or rodent models of diabetes, whereas chrononutrition-related interventions include eating windows, breakfast skipping, nocturnal and evening eating. Primary outcomes are circadian rhythm biomarkers, composition and diversity of gut microbiota and cardiometabolic parameters. We will use validated tools tailored to each study design to assess methodological quality and risk of bias in the studies. Results will be integrated narratively, followed by meta-analysis where appropriate. Registration: INPLASY; Registration ID: INPLASY2025110030.