The body’s internal clock, known as the circadian rhythm, is well established as a key regulator of digestive system function. A new review from researchers at Baylor College of Medicine has examined how lesser-known elements, called noncanonical clock regulators, play a role in how digestive organs respond to stress. Their findings were published in Trends in Endocrinology and Metabolism.
Everyday habits such as shift work, travel across time zones, or eating meals at irregular hours can disrupt natural body rhythms. These disruptions have been linked to stress responses in the digestive system that may lead to disorders.
“By focusing on these overlooked clock factors, the paper integrates new findings into the bigger circadian (daily rhythm) picture and highlights how timing-based strategies, like eating or taking medicine at specific times of day (known as chronotherapy) might help keep our digestive health on track,” said Dr. Dongyin Guan, assistant professor of medicine-endocrinology at Baylor and author of the paper.
Research shows that persistent disturbances in daily rhythms are associated with issues such as fatty liver disease, inflammatory bowel diseases, and metabolic conditions including diabetes. Experts emphasize that keeping regular sleep and meal schedules supports gut health.
The review analyzed results from multiple studies addressing various sources of stress—including high-fat diets, altered mealtimes, physical activity changes, and aging—and their effects on gene activity patterns and metabolism within digestive organs.
“By piecing together data from all these studies, we built and updated how these noncanonical clock regulators work alongside the core clock,” said Dishu Zhou, research assistant in the Dongyin Guan Lab at Baylor and corresponding author of the paper.
Even when primary clock genes were disabled in laboratory models, most genes kept their daily cycles running—suggesting other factors help maintain biological timing under challenging conditions. The review found that noncanonical regulators link timing mechanisms to cellular stress response pathways. These backup systems activate during stressful events or unusual routines to preserve essential cycles despite lifestyle disruptions.
Researchers suggest these additional regulators could become targets for new therapies if they prove vital within specific organs. They also point out that aligning behaviors such as eating or medication intake with one’s natural rhythms may benefit digestive health—a strategy called chrononutrition or chronopharmacology—which could offer practical ways to reduce strain on the digestive tract.
“Doctors might be able to use these insights to advise patients on aligning meals and medication schedules with their natural body clocks,” Guan said. “Given how common circadian disruptions are, this timing-focused approach could become a powerful tool to boost digestive health and overall well-being.”
Future studies will explore whether genetic differences or personal habits influence how people’s internal clocks operate—potentially affecting susceptibility to digestive problems. The team also plans to develop wearable sensors or blood tests for real-time monitoring of individual biological rhythms so healthcare providers can tailor nutrition plans or drug regimens accordingly.
“The research is moving toward personalized medicine. By understanding each person’s internal clock, we can customize treatments and daily schedules to keep their digestive system and overall health in sync,” Guan said.
This publication marks the first comprehensive review connecting noncanonical clock regulators with stress responses involved in digestive diseases.
“By respecting that natural cycle, whether through smarter scheduling of eating and taking medicine or simply getting good sleep, we could vastly improve our digestive health and quality of life,” Guan said.
Other contributors include Roberto E López-Valiente and Samer G. Mattar. The project received support from organizations such as CPRIT Scholar in Cancer Research (RR210029), V Foundation (V2022-026), NIH R37CA296577, DK056338, P30-CA125123, TRISH NNX16AO69A and H-NORC.
