Circadian disruption, gut microbiome changes linked to colorectal cancer progression

Irvine, Calif., Sept. 27, 2024 — Research from the University of California, Irvine has revealed how disruption of the circadian clock, the body’s internal, 24-hour biological pacemaker, may accelerate the progression of colorectal cancer by affecting the gut microbiome and intestinal barrier function. This discovery offers new avenues for prevention and treatment strategies.

The study, published online today in the journal Science Advances, offers a more comprehensive understanding of how important changes occur in the function and composition of the gut microbiome when the circadian clock is disturbed in the presence of colorectal cancer.

“There is an alarming rise in early-onset colorectal cancer in adults under the age of 50,” said corresponding author Selma Masri, associate professor of biological chemistry. “Circadian misalignment through extended light exposure, late-night meals and other environmental factors could [be] driving these cases. Our study suggests that clock disruption, particularly through lifestyle choices, may play a significant role in gut health and, subsequently, cancer risk.”

Previous research has shown that disturbances to the circadian clock can influence the progression of colorectal cancer, but until now, how the biological clock and cancer impact the gut microbiome was unclear. Using colorectal cancer mouse models, the team found that when the circadian clock is disrupted, the diversity and abundance of gut bacteria change, and this is further exacerbated by cancer development.

Researchers also identified notable alterations in the microbial pathways involved in the metabolism of nucleic acids, amino acids and carbohydrates. These functional changes were linked to reduced levels of intestinal mucus, which normally protects the gut lining from harmful bacteria, suggesting that the circadian clock is crucial for maintaining barrier integrity. Increased permeability of the intestinal lining allows toxins and bacteria to enter the bloodstream, potentially accelerating cancer progression.

“While these findings are important, more work needs to be done,” Masri said. “In particular, we now want to know if changes in the timing and abundance of certain gut bacteria could directly lead to colorectal cancer development over time. Long-term studies will be critical in determining whether circadian misalignment drives cancer and how we might prevent it in the future. 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.”

The study was led by Rachel Fellows, a postdoctoral fellow in biological chemistry. Other team members included Assistant Professors Marcus M. Seldin and Nicholas R. Pannunzio; postdoctoral fellow Sung Kook Chun; graduate students Alisa L. Mahieu, Bridget Fortin and Wei A. Song; and associate specialist Natalie Larson – all from the School of Medicine’s Department of Biological Chemistry.

This work was supported by grants from the National Institutes of Health, the Concern Foundation and Johnson & Johnson, among others. See the study for a full list.

About the University of California, Irvine: Founded in 1965, UC Irvine is a member of the prestigious Association of American Universities and is ranked among the nation’s top 10 public universities by U.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UC Irvine has more than 36,000 students and offers 224 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UC Irvine, visit www.uci.edu.

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