昼夜节律紊乱与结直肠癌肝转移:肠道菌群-免疫轴的调控作用及研究进展OA

Approximately 50％of patients with colorectal cancer(CRC)develop liver metastases,with circadian rhythm disruption serving as a significant risk factor;however,the synergistic regulatory mechanisms between the gut microbiota and immune microenvironment remain incompletely elucidated.In recent years,the"gut microbiota-immune axis"has provided a novel theoretical framework for dissecting this process.Circadian rhythm disruption increases the abundance of Enterobacteriaceae while decreasing that of Roseburia and Akkermansia,accompanied by aberrant accumulation of deoxycholic acid(DCA)and taurocholic acid(TCA).DC A directly suppresses the cytotoxic function of CD8+T cells via the plasma membrane Ca2+-transporting ATPase-nuclear factor of activated T cells 2(PMCA-NFAT2)pathway,whereas TCA drives the hepatic recruitment of neutrophils and myeloid-derived suppressor cells(MDSCs),which collaboratively establish an immunosuppressive pre-metastatic niche.This paper systematically reviewed the core regulatory pathways and research progress of circadian rhythm disorders driving colorec-tal cancer liver metastasis(CRLM)via the gut microbiota-immune axis.Chronotherapy,probiotic inter-ventions,and fecal microbiota transplantation(FMT)based on this axis are highlighted as promising new directions for CRLM prevention and treatment.However,discrepancies between human and murine microbiota,along with the immune heterogeneity of liver metastases,remains key bottlenecks for clinical translation.