Circadian rhythms play a pivotal role in regulating diverse physiological functions, notably the composition and activity of gut microbiota. Accumulating evidence indicates that circadian rhythm disruption can induce dysbiosis of the gut microbiome, which in turn is implicated in influencing the tumor microenvironment (TME) and facilitating cancer progression.

jahanzeb-ahsan-CRhYo_0E2AY-unsplash

This review integrates and analyzes recent advances elucidating the complex interplay where circadian rhythms modulate gut microbiota, and how these circadian-driven microbial changes affect the TME. This review analyzes recent advances in elucidating the complex interplay among circadian rhythms, gut microbiota, and the TME.

READ MORE: Researchers uncover role of fungal circadian clock in pathogenicity

READ MORE: Circadian disruption and gut microbiome changes linked to colorectal cancer progression

The authors examine how circadian disruption modifies the diversity and metabolic functions of gut microbiota, resulting in alterations of microbial metabolites, including but not limited to short-chain fatty acids and secondary bile acids. These metabolic alterations have the potential to modulate immune cell function, vascular remodeling, and tumor cell metabolism within the TME.

The study investigates the potential mechanisms through which gut microbial dysbiosis induced by circadian misalignment could promote an immunosuppressive TME and accelerate tumor growth. Additionally, it evaluates emerging therapeutic strategies that leverage the circadian-microbiome axis, encompassing chronotherapy, probiotic supplementation, and fecal microbiota transplantation.

Low-Res_图片2

Source: Qinglong Xu

Dysbiosis of the gut microbiota compromises intestinal mucosal barrier function, primarily characterized by downregulation of tight junction proteins in intestinal epithelial cells, consequently increasing intestinal permeability. This enhanced permeability facilitates the translocation of potentially pathogenic bacteria into intestinal tissues, initiating inflammatory cascades that promote tumor proliferation and microvascular remodeling. Concurrently, increased lactate levels in the intestinal microenvironment contribute to tumor proliferation and induce the accumulation of tumor-associated macrophages and dendritic cells, further fostering a pro-tumorigenic microenvironment. Probiotic intervention has the potential to restore intestinal homeostasis, as evidenced by enhanced tight junctions between intestinal cells, increased goblet cell populations, and mucosal layer repair. In the tumor microenvironment, this intervention results in a reduction of regulatory T cells, attenuation of pro-inflammatory factors, augmentation of CD8+ T cell activity, and diminished presence of various myeloid-derived suppressor cell subtypes. These orchestrated changes synergistically modulate the microenvironment, culminating in the suppression of tumor growth.

The integration of circadian biology, microbiology, and cancer immunology presents promising avenues for the development of novel diagnostic and therapeutic approaches. However, significant challenges persist in translating these findings into viable clinical applications. Further research is imperative to elucidate the molecular pathways interconnecting circadian rhythms, gut microbiota, and the TME, and to develop personalized chronobiological interventions for cancer prevention and treatment. 

Topics