Circadian Disruption Linked to Colorectal Cancer Progression

Research from the University of California, Irvine (UCI) has identified a significant link between the disruption of the circadian clock and the progression of colorectal cancer (CRC), mediated by changes in the gut microbiome and intestinal barrier function. This discovery offers potential new strategies for prevention and treatment.

Background and Study Overview

The study, published in Science Advances, demonstrates how the disruption of circadian rhythms leads to alterations in the gut microbiome and negatively affects the intestinal barrier in the presence of colorectal cancer^[1]. These findings shed light on the mechanisms through which circadian misalignment may contribute to CRC progression.

"There is an alarming rise in early-onset colorectal cancer in adults under the age of 50," said Dr. Selma Masri, the study's corresponding author and Associate Professor of Biological Chemistry at UCI.
"Circadian misalignment through extended light exposure, late-night meals, and other environmental factors could drive these cases."

Key Findings and Impact of Circadian Disruption

The research team utilized colorectal cancer mouse models to study the effects of circadian disruption on the gut microbiome. Key findings include:

1. Altered Microbial Diversity and Abundance
   Disruption of the circadian clock led to notable changes in both the diversity and abundance of gut bacteria. These changes were more pronounced in the presence of cancer development.
2. Pathway Alterations in Gut Microbes
   Changes were observed in microbial pathways involved in the metabolism of nucleic acids, amino acids, and carbohydrates. These pathways are essential for gut function and health.
3. Decreased Intestinal Mucus and Barrier Integrity
   The disrupted circadian clock was associated with reduced levels of intestinal mucus, impairing the gut's protective lining and potentially allowing harmful bacteria and toxins to pass into the bloodstream. This breakdown of the intestinal barrier may accelerate cancer progression.

Future Directions: Long-term Studies and Preventive Strategies

The UCI team emphasized that while these findings are significant, more research is needed to establish the direct effects of changes in gut microbiota on colorectal cancer development over time. Future long-term studies will be crucial in determining whether circadian misalignment is a causative factor in CRC development and how it might be prevented.

"Deeper insights into how the body's internal clock shapes the gut's ecosystem could pave the way for treatments that not only address cancer but also improve overall gut health," said Dr. Masri.

Research Team and Acknowledgments

The study was led by Rachel Fellows, a postdoctoral fellow in biological chemistry at UCI. Additional contributors included Assistant Professors Marcus M. Seldin and Nicholas R. Pannunzio, postdoctoral fellow Sung Kook Chun, and graduate students Alisa L. Mahieu, Bridget Fortin, and Wei A. Song. Natalie Larson, an associate specialist, also contributed to the research.

Reference

Journal Information: Science Advances
Provided by: University of California, Irvine

1. Fellows, R. C., et al. (2024). Disruption of the intestinal clock drives dysbiosis and impaired barrier function in colorectal cancer. Science Advances. DOI: 10.1126/sciadv.ado1458. ↩︎