Research has uncovered how disruptions to the circadian clock, which serves as the body’s internal 24-hour biological timer, may speed up the progression of colorectal cancer by impacting the gut microbiome and the integrity of the intestinal barrier. This finding opens up new possibilities for prevention and treatment methods.
Research has uncovered how disruptions to the circadian clock, which serves as the body’s internal 24-hour biological timer, may speed up the progression of colorectal cancer by impacting the gut microbiome and the integrity of the intestinal barrier. This finding opens up new possibilities for prevention and treatment methods.
The research, published today in the journal Science Advances, provides a deeper insight into how significant changes in the function and composition of the gut microbiome occur when the circadian clock is disturbed in the context of colorectal cancer.
“There is a concerning increase in early-onset colorectal cancer among adults under 50,” stated Selma Masri, the study’s lead author and an associate professor of biological chemistry. “Circadian misalignment, caused by factors like prolonged exposure to light, late-night eating, and other environmental conditions, could be contributing to these cases. Our findings suggest that disruptions to the circadian rhythm, especially due to lifestyle habits, may significantly affect gut health and, consequently, cancer risk.”
While previous studies have indicated that disturbances to the circadian rhythm can affect colorectal cancer progression, the specific mechanisms by which the biological clock and cancer relate to the gut microbiome were previously unclear. Utilizing mouse models of colorectal cancer, researchers discovered that when the circadian clock is disturbed, there is a change in the diversity and quantity of gut bacteria, which is even more pronounced during cancer development.
The team also observed significant changes in the microbial pathways involved in processing nucleic acids, amino acids, and carbohydrates. These functional alterations were connected to a decrease in intestinal mucus levels, which usually serves to shield the gut lining from harmful bacteria, implying that the circadian clock is essential for preserving barrier integrity. An increase in the permeability of the intestinal lining enables toxins and bacteria to enter the bloodstream, potentially hastening cancer progression.
“While these findings are significant, more research is necessary,” Masri emphasized. “We particularly want to investigate if variations in the timing and quantity of specific gut bacteria could directly contribute to the development of colorectal cancer over time. Long-term studies will be vital in establishing whether circadian misalignment promotes cancer and how we could prevent it moving forward. Gaining a deeper understanding of how the body’s internal clock influences the gut ecosystem could lead to treatments that not only target cancer but also enhance overall gut health.”
The study was spearheaded by Rachel Fellows, a postdoctoral fellow in biological chemistry. Other contributors 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, along with associate specialist Natalie Larson, all affiliated with the School of Medicine’s Department of Biological Chemistry.
This research received support from various grants, including those from the National Institutes of Health, the Concern Foundation, and Johnson & Johnson, among others.
