How do stress, sleep, gut imbalances affect it?

• Stress and working at night are both known to affect cancer risk, including colorectal cancer risk.
• Colorectal cancer risk and progression have both been linked to the microbiome, dysregulation of which has been linked to stress and disruption of the circadian rhythm.
• Recent research in mice has linked stress and a disrupted circadian cycle to disruption of the gut microbiome, and suggested that this may contribute to colorectal cancer progression due to its impact on intestinal permeability and inflammation.

The impact of circadian rhythm and stress on the gut microbiome and colorectal cancer progression are the focus of recent research.

Researchers have found that colorectal cancer is exacerbated by disruption to the circadian rhythm, which contributes to changes in the gut microbiome that can increase intestinal permeability, which in turn increases inflammation, which can lead to the progression of colorectal cancer.

These were the findings of a study in mouse models of colorectal cancer, which appeared in Science Advances in September 2024.

Stress can also impact the microbiome, having an impact on colorectal cancer progression in mice, findings presented at the United European Gastroenterology (UEG) Week 2024 — held in Vienna, Austria — which are yet to be published in a peer-reviewed journal, showed.

Both of these studies used mouse models that had been genetically modified to mimic certain conditions, including tendency towards forming tumours or circadian disruption.

The stress of sleep disruption and impact on the circadian cycle could both have significant impacts on various homeostatic processes, Shuji Ogino, MD, PhD, professor of pathology at Harvard Medical School and Brigham and Women’s Hospital, told Medical News Today.

Ogino, who was not involved in either of these studies, said he viewed “night shift work being accepted as a carcinogen,” and pointed to hormonal disturbances and interference with anticarcinogenic and anti-inflammatory processes that could be caused by disrupted sleep.

“I think the sleep disturbance and the hormonal disturbance likely impair those cancer suppression mechanisms. They may also derange some growth factors, maybe upregulating them,” he added.

“Sleep disruption may interfere in gut homeostasis. So we have a sympathetic nervous system and a parasympathetic nervous system. When we are awake we have an activated sympathetic nervous system so that we can fight or run. When we sleep, different neuronal and endocrine homeostatic mechanisms play and regulate our body including intestines with abundant microbes. We have kept such a circadian rhythm over thousands of years.”

– Shuji Ogino, MD, PhD

Researchers from Prof. Jinlin Yang’s research group in the Department of Gastrointestinal Cancer and Liver Diseases, West China Hospital, Sichuan University of China, who presented their findings at UEG Week 2024, used mouse models induced to develop colorectal cancer.

The split the mice in different groups. One group was exposed to chronic stress, using restraints. Then, researchers carried out fecal transplants to investigate the impact of stress on the microbiome and colorectal cancer development.

Researchers found that mice receiving fecal transplants from the chronic stress group exhibited a higher tumor burden compared to those that had received fecal transplants from controls.

This suggested that the impact of chronic stress impacts the gut microbiota in a way that is involved in the progression of colorectal cancer.

Lead researcher Qing Li, PhD, a postdoctoral researcher in Professor Jinlin Yang’s research group, explained the study premise to MNT:

“In mouse model[s], we performed fecal microbiota transplantation […] and found that fecal microbiota transplantation from stressed mice promote the progression of colorectal cancer. However, after [the] eradication of gut microbiota by using [an] antibiotic cocktail, there was no difference in tumor formation between [the] control [group] and [the] stressed group. These results highlight the crucial role of gut microbiota during chronic stress in promoting colorectal cancer progression.”

Further analysis showed that certain strains of bacteria, particularly Lactobacillus bacterial strains, which researchers believe to be beneficial, were lower in the chronic stress group. There was also lower activity of some antitumor immune cells in this group.

“The initial motivation for this study stemmed from our frequent observations in clinical work that the mental state of cancer patients influences their prognosis,“ said Li.

“Patients who were excessively worried about their condition often had poorer outcomes. This prompted me to review the literature on how this state affects colorectal cancer patients. During the literature review, I discovered that chronic stress can alter the gut microbiota, but it remains unclear whether these changes in the microbiota can promote colorectal cancer progression,” he added.

Li suggested that the study had also identified a potential target for colorectal cancer prevention.

“We found that supplementing with Lactobacillus plantarum during chronic stress can inhibit colorectal cancer progression. I believe this could potentially become an intervention strategy for chronic stress related colorectal cancer treatment, while the mechanism behind this needs to be elucidated,” he told us.

In the study published in Science Advances, researchers used two types of genetically engineered mouse model, one that had been genetically engineered to be predisposed to developing tumors, the other genetically engineered to have its circadian rhythm — which involves sleep/wake cycle regulation — disrupted.

The researchers further bred the colorectal cancer-predisposed mice with the circadian rhythm-disrupted mice in order to obtain offspring who were both predisposed to cancer and to poor sleep/wake cycle regulation.

When circadian disruption was combined with colorectal cancer, researchers discovered and the diversity of the microbiome changed, affecting metabolite pathways and the junctions that control the permeability of the intestine did not function as well as usual.

The researchers thought this could contribute to inflammation in the gut, which in turn contributes to the progression of colorectal cancer.

Anton Bilchik, MD, PhD, surgical oncologist, chief of medicine, and director of the Gastrointestinal and Hepatobiliary Program at Providence Saint John’s Cancer Institute in Santa Monica, CA, who was not involved in either of these studies, told MNT that the one published in Science Advances “is a very provocative study that demonstrates that disruption in the circadian clock leads to alterations in the gut microbiome and immune microenvironment.“

“Although not causally demonstrated in this study, these alterations may increase the risk of getting colorectal cancer and potentially other cancers as well. Given the unexplained increase in early onset colorectal cancer this may present a possible explanation in young patients although many additional studies need to be performed,” he suggested.