Disruption of the intestinal clock drives dysbiosis and impaired barrier function in colorectal cancer

被引:3
作者
Fellows, Rachel C. [1 ]
Chun, Sung Kook [1 ]
Larson, Natalie [1 ]
Fortin, Bridget M. [1 ]
Mahieu, Alisa L. [1 ]
Song, Wei A. [1 ]
Seldin, Marcus M. [1 ,2 ]
Pannunzio, Nicholas R. [1 ,2 ,3 ]
Masri, Selma [1 ]
机构
[1] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA
来源
SCIENCE ADVANCES | 2024年 / 10卷 / 39期
基金
美国国家科学基金会;
关键词
NIGHT-SHIFT WORK; CIRCADIAN CLOCK; GUT MICROBIOTA; FUSOBACTERIUM-NUCLEATUM; CELL-CYCLE; DIETARY FIBER; MUCUS BARRIER; COLON-CANCER; RISK; EXPRESSION;
D O I
10.1126/sciadv.ado1458
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Apc-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 Bacteroides, Helicobacter, and Megasphaera. 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.
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页数:16
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