Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, 92697, USA.
Sci Adv. 2024 Sep 27;10(39):eado1458. doi: 10.1126/sciadv.ado1458.
Diet is a robust entrainment cue that regulates diurnal rhythms of the gut microbiome. We and others have shown that disruption of the circadian clock drives the progression of colorectal cancer (CRC). While certain bacterial species have been suggested to play driver roles in CRC, it is unknown whether the intestinal clock impinges on the microbiome to accelerate CRC pathogenesis. To address this, genetic disruption of the circadian clock, in an driven mouse model of CRC, was used to define the impact on the gut microbiome. When clock disruption is combined with CRC, metagenomic sequencing identified dysregulation of many bacterial genera including , , and We identify functional changes to microbial pathways including dysregulated nucleic acid, amino acid, and carbohydrate metabolism, as well as disruption of intestinal barrier function. Our findings suggest that clock disruption impinges on microbiota composition and intestinal permeability that may contribute to CRC pathogenesis.
饮食是调节肠道微生物组昼夜节律的有力的时间信号。我们和其他人已经表明，生物钟的破坏会导致结直肠癌（CRC）的进展。虽然已经有一些细菌物种被认为在 CRC 中起驱动作用，但尚不清楚肠道生物钟是否会影响微生物组以加速 CRC 的发病机制。为了解决这个问题，在 CRC 的驱动小鼠模型中，通过遗传破坏生物钟来定义对肠道微生物组的影响。当时钟破坏与 CRC 结合时，宏基因组测序确定了许多细菌属的失调，包括、、和。我们确定了微生物途径的功能变化，包括失调的核酸、氨基酸和碳水化合物代谢，以及肠道屏障功能的破坏。我们的研究结果表明，时钟破坏会影响微生物群落组成和肠道通透性，这可能有助于 CRC 的发病机制。
