This study shows that stress, daily biological (circadian) rhythms, and the gut microbiota, that is, the microorganisms that live in the intestine, are closely linked. These three elements interact to help the body respond and adapt to external factors, such as changes in the environment and stressful situations.
The circadian rhythm is like a "biological clock" that controls the body's activities throughout the day, while the stress response prepares the body to face threats or changes. These two systems are distinct, but their communication pathways in the body have significant overlap.
Both depend on a circuit called the HPA (hypothalamic-pituitary-adrenal) axis, which, when activated, releases hormones called glucocorticoids (such as cortisol) to help the body respond to stress.
This system also coordinates essential circadian activities, such as the transition between sleep and wakefulness, signaling the start of the day and preparing the body for a new daily journey.
In addition to influencing digestion and immunity, gut microbes appear to affect both stress and circadian rhythm. Studies show that the composition and activity of the gut microbiota change throughout the day.
These rhythmic fluctuations are important for the stability of the circadian rhythm and for maintaining proper control of the stress response. When the gut microbiota is altered or weakened, the body’s response to stress is impaired, which also affects the balance of activities controlled by the circadian rhythm.
To understand these interactions, researchers at University College Cork studied mice without gut microbes (‘germ-free’ mice). They found that these mice had altered levels of glucocorticoids, and their responses to stress were exaggerated.
Furthermore, these changes were linked to a “mismatch” in the function of neurons that regulate circadian rhythm and stress. By replacing the microbiota in these mice, it was possible to restore some aspects of these responses.
The study demonstrated that the absence of microbiota interferes with the normal rhythms of the HPA axis. The natural oscillations of glucocorticoids, which vary according to the time of day, were altered, which directly impacted the stress and social behaviors of the mice.
These effects were further influenced by a specific bacterial strain, Lactobacillus reuteri, which, when reintroduced, helped to regulate the stress response and glucocorticoid levels.
Lactobacillus reuteri
The results suggest that our gut microbiota plays a crucial role in regulating our circadian rhythms and how we respond to stress. When these microorganisms are out of balance, we may experience changes in how our bodies deal with stress throughout the day, which can impact other processes, such as immunity and metabolism.
In summary, the study suggests that gut microorganisms are essential for synchronizing our “biological clock” with our stress response. These microorganisms maintain the balance of the circadian system and glucocorticoids, allowing the body to respond adaptively to stress and sustain metabolic health.
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Gut microbiota regulates stress responsivity via the circadian system
Gabriel S.S. Tofani, Sarah-Jane Leigh, Cassandra E. Gheorgh, Thomaz F.S. Bastiaanssen, Lars Wilmes, Paromita Sen, Gerard Clarke, John F. Cryan.
Cell metabolism. November 5, 2024.
Abstract:
Stress and circadian systems are interconnected through the hypothalamic-pituitary-adrenal (HPA) axis to maintain responses to external stimuli. Yet, the mechanisms of how such signals are orchestrated remain unknown. Here, we uncover the gut microbiota as a regulator of HPA-axis rhythmicity. Microbial depletion disturbs the brain transcriptome and metabolome in stress-responding pathways in the hippocampus and amygdala across the day. This is coupled with a dysregulation of the circadian pacemaker in the brain that results in perturbed glucocorticoid rhythmicity. The resulting hyper-activation of the HPA axis at the sleep/wake transition drives time-of-day-specific impairments of the stress response and stress-sensitive behaviors. Finally, microbiota transplantation confirmed that diurnal oscillations of gut microbes underlie altered glucocorticoid secretion and that L. reuteri is a candidate strain for such effects. Our data offer compelling evidence that the microbiota regulates stress responsiveness in a circadian manner and is necessary to respond adaptively to stressors throughout the day.
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