It has long been known that sleep deprivation weakens the immune system. Now, researchers at the University of Florida Health Cancer Institute have made the surprising discovery that the gut microbiome drives changes in the immune system caused by chronic sleep deprivation. These changes accelerate cancer progression, disrupt circadian rhythms, and make chemotherapy less effective.
“Sleep deprivation is extremely common among cancer patients, but is often overlooked in patient care, and there has been a lack of molecular evidence linking it to disease outcomes,” said Maria Hernandez, a graduate student in Dr. Christian Jobim’s lab, who presented the study at the American Association for Cancer Research 2026 Annual Meeting on April 20 in San Diego.
This study highlights the importance of maintaining a healthy microbiome through quality sleep and a healthy diet. Our findings are of great importance because they highlight the need to assess patients as a whole and identify ways in which these systems can be better supported to improve patient outcomes. ”
Maria Hernandez, University of Florida
The intestinal flora is a collection of trillions of microorganisms, including bacteria that live in the intestines. It is known to be intricately interconnected with the immune system. Jobim’s team wanted to know whether sleep deprivation affects the microbiome in ways that promote cancer progression and poor treatment response.
Researchers used a mouse model to mimic the effects of long-term sleep deprivation in humans. They collected stool samples from sleep-deprived mice and transplanted them into healthy mice whose microbiota had been wiped out, allowing them to precisely examine the role of the microbiome.
The researchers measured tumor growth and response to 5-FU, the most common chemotherapy drug given to colorectal cancer patients. 5-FU is now the deadliest cancer for people under 50 in the United States. They compared immune cell populations in the tumor microenvironment, genes involved in regulating circadian rhythms, and other immune markers in sleep-deprived and normal mice.
The researchers found that sleep-deprived mice not only had worse cancer progression as measured by tumor volume, but also had chemotherapy drugs become less effective and the amount of immune cells involved in anti-tumor immunity reduced. Genes that regulate circadian rhythms were also affected.
“We think that sleep deprivation changes the composition of the microbiome, which in turn changes the behavior of the bacteria,” Hernandez said. “We have shown that these changes have functional implications for both cancer progression and cancer treatment. There is something happening in the microbiome that is causing the treatment to be less effective.”
The research team is working to determine the mechanism and identify the specific molecules involved. This study highlights the importance of collecting sleep data in large groups of human patients so that changes in the microbiome can be compared over time, said Jobim, co-leader of the UF Health Cancer Institute’s Immuno-Oncology and Microbiology Research Program.
The good news? The microbiome is “plastic” and can change due to lifestyle changes.
“We know a lot about the microbiome, so we need to take care of it and treat it with respect,” said Jobim, the Gatorade Distinguished Professor at the University of Florida School of Medicine. “As your mom used to say, sleep is important, eat well. We understand this holistically, but now we know it can be through your microbiome. It can be something that is in tune with your lifestyle.”
Of course, it’s not always possible to get a good night’s sleep, especially for patients who have been hospitalized for a long time or are undergoing cancer treatment.
In the long term, the new findings will pave the way for researchers to develop ways to rebalance the microbiome, including restoring “good bacteria” and creating targeted drugs. Jobim’s lab has pioneered new ways to unlock the therapeutic potential of the microbiome and recently identified druggable molecules that enhance cancer treatment responses. Similar techniques can be applied to target changes induced by sleep disruption.
