How gut bacteria regulate stress and sleep cycles

Gut Microbiota’s Role in Circadian Rhythms and Stress Responses: Potential Insights for Treating Stress-Related Disorders

A recent study published in Cell Metabolism explores how gut microbiota influences the body’s circadian rhythms and stress responses. Researchers focused on the hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress response patterns throughout the day, suggesting that gut bacteria might impact how we respond to stress at different times.

How Gut Microbiota Affects Stress

The stress and circadian systems interact closely through the HPA axis and the autonomic nervous system. Stress triggers an immediate response to potential threats, while circadian rhythms anticipate changes in the environment, creating a balance. Glucocorticoids—key hormones in both systems—follow daily rhythms controlled by the brain’s central clock, the suprachiasmatic nucleus (SCN). This rhythm means stress responses vary, typically showing more resilience during peak periods.

The gut microbiota influences brain function through the HPA axis, particularly affecting stress-related regions like the hippocampus and amygdala. Bacterial cycles in the gut support metabolic health, but disruption can lead to irregular glucocorticoid levels and altered stress responses.

Study Overview

In this study, scientists evaluated gut microbiota’s effect on HPA-axis function in mice, using antibiotic treatment and germ-free conditions to deplete microbiota. They used fecal microbiota transplantation (FMT) and measured responses to stress through blood glucose, corticosterone levels, and behavior. Researchers also collected samples from brain regions involved in stress and circadian regulation and analyzed them for gene expression.

Plasma levels of stress-related hormones were measured at various times, while DNA sequencing and metabolomics provided insights into microbial influences on stress responses. Multi-omics and statistical analyses helped map gut-brain interactions.

Key Findings

The study found that gut bacteria, especially Lactobacillus reuteri, play a significant role in regulating corticosterone rhythms. In microbiota-depleted mice, corticosterone release patterns shifted, reflecting disruptions in natural circadian rhythms. In germ-free (GF) mice, the peak of corticosterone secretion moved to nighttime, while in antibiotic-treated (ABX) mice, secretion increased unpredictably. These shifts corresponded with altered gene expression in brain regions associated with stress and circadian regulation, possibly heightening vulnerability to stress-related conditions.

Disruptions in gut microbiota affected brain metabolism, especially in glutamate pathways vital for stress responses, and altered stress-related behaviors. Mice with typical corticosterone rhythms displayed normalized behaviors after stress exposure, confirming gut bacteria’s role in stress regulation.

Conclusions

This study highlights the gut microbiota’s influence on stress responses and circadian rhythms, pointing to potential pathways for addressing stress-related disorders. Further research is needed to pinpoint microbial signals that impact stress hormones and to understand how these findings may be applicable to humans.