First, they noted that there is a lot of overlap between the body’s circadian system and its stress response. The circadian rhythm refers to the regulation of basic bodily functions, such as sleep-wake cycles, that happen throughout a 24-hour day.

The stress response — “characterized as a rapid adaptive process to actual or perceived danger,” as the researchers note in their paper — can significantly affect circadian rhythm, as previous studies have shown.

The authors of the recent study further explained that one of the key pathways that helps with information regarding circadian rhythm and stress response is the hypothalamic-pituitary-adrenal (HPA) axis. This pathway is also central to how bacteria in the gut can affect both behavior and how the brain works.

Researchers used germ-free and conventional mice to help study the complex relationship between gut microbiota and the stress response. They collected data from components like blood samples, brain imaging, behavioral testing, and tissue analysis.

They were able to use control mice to find that the gut microbiota varies throughout the day. The researchers depleted some mice’s gut microbiota using antibiotics and looked at germ-free mice.

In studying these mice, they found that this microbiota depletion affected the daily rhythm of corticosterone levels in the mice’s plasma. The human equivalent of corticosterone is cortisol, a glucocorticoid. Glucocorticoids are central to the stress response and circadian rhythms.

Further analysis of mice also suggested that gut bacteria influence central circadian rhythmicity. Results further indicated that gut bacteria changes may change the rhythm of stress pathways in parts of the brain that regulate “the stress response,” and that microbial depletion changes the 24-hour rhythms of the HPA axis.

Next, the researchers were interested in seeing how mice responded to stress based on the time of day and microbiota depletion.

After exposure to stress, mice with depleted gut microbiota did not have an increase in corticosterone at a specific time of day like the control mice did.

Similarly, the mice with microbial depletion experienced no changes to their social interactions after the stress exposure at a specific time of day. In contrast, the control group experienced a decrease in interaction with other mice. At the other time of day measurement, the groups behaved similarly.

They also found that mice with microbial depletion experienced changes in gut bacteria throughout the day. It suggested that this time-specific change is associated with time-specific increases in corticosterone in plasma, which is a blood component.

Based on fecal microbial transplant data, researchers also found that the bacterial species Limosilactobacillus reuteri may be the key to changes in corticosterone levels.

Overall, the results indicated that the gut microbiota likely plays a key role in the stress response “in a circadian manner.”

Marc J. Tetel, PhD, chair and Allene Lummis Russell professor in neuroscience at Wellesley College in Massachusetts, who was not involved in this study, commented with his thoughts on the study’s findings to Medical News Today.

According to him:

“The recent paper […] provides compelling and exciting evidence that gut microbiota can regulate both the stress and circadian systems in a coordinated fashion through the gut-brain axis. Recognizing how the stress and circadian systems interact and are impacted by gut microbiota is critical to better understanding the role of these systems in a variety of mental health disorders, including anxiety and depression.”

Some questions remain as to whether and how these findings might apply to humans, since this research was conducted in mice.

Research in people can add to the data in this area and possibly confirm this study’s findings. In their paper, the authors noted that studying these concepts in people from different areas who follow various diets and lifestyle patterns will be useful.

There are also aspects of the research that open up further questions. For example, the researchers would also be interested in discovering how gut microbiota signals reach the brain.

Emeran Mayer, MD, director of the UCLA Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, professor of psychology medicine, and codirector of CURE: Digestive Diseases Research Center, who was not involved in this research, told MNT that “the findings of the […] study shows the possible causality between gut microbial changes and central stress responsiveness, and identify L. Reuteri as a possible organism involved.”

He also emphasized that “the findings and conclusions are intriguing but the question remains how much of it is translatable to humans.”

“Even long-term broad-spectrum antibiotic treatment or the consumption of the probiotic L. Reuteri in humans, to my knowledge, does not significantly affect stress responsiveness,” Mayer explained.

“Furthermore, the stress response to everyday stressors is mainly mediated by the sympathetic nervous system and not by the HPA axis, an aspect not addressed in this study. As many of the intriguing data coming from such mouse studies, there is need for caution when extrapolating the findings to human health and disease,” he added.

While more research is needed, people can take steps to look after gut health as a key component of overall well-being. This could include steps like eating fermented foods and cutting back on sugar.

People should seek help from their primary care doctors and other experts to determine what steps toward better gut health would be most beneficial for them.

David Merrill, MD, PhD, a board-certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health, who was not involved in the recent research, advised that:

“We can support a healthy gut microbiome with dietary changes rich in fiber and prebiotic foods like bananas, onions, and oats, which help feed beneficial bacteria. For supplements, probiotics containing Lactobacillus or Bifidobacterium strains show promise to positively impact mood and stress responses by enhancing microbial diversity.”

However, caution is warranted. Mayer told us that: “Before data from well designed human studies are available to confirm the above hypotheses, I don’t believe recommendations for specific diets or supplements aimed to normalize an exaggerated stress responsiveness should be made.”

“However, there is already a wealth of clinical data supporting many health benefits for a largely plant based diet, and this information has been incorporated in the new field of Nutritional Psychiatry,” he pointed out.