Dysfunctional circadian-driven dynamics in gut microbiota and tumor microenvironment

Circadian rhythms govern physiological activities through the precise modulation of gene expression and biochemical functions. Dysfunction of circadian rhythms is associated with an increased risk of tumor formation, growth, and metastasis, as well as alterations in the gut microbiota (GM) and the tumor microenvironment (TME). Indeed, the intricate regulatory interactions between the circadian system, GM, and TME present a promising area for further exploration. This review, centered on the circadian system, focuses on the dynamics in the GM and the TME driven by circadian dysfunction. Additionally, it places particular emphasis on the interplay between circadian rhythms and GM. The review further explores how this interplay can be therapeutically leveraged to normalize the TME and enhance clinical outcomes. For the first time, the rhythms-microbiota-microenvironment axis is proposed, linking the circadian system, GM, and TME. Circadian dysfunction significantly impacts this axis, leading to disruptions in both the GM and TME. The review also provides the latest insights and innovative therapies from the perspective of the interplay between circadian rhythms and GM.