A recent study published in Cell Metabolism explores how gut microbiota influences the body’s stress response, particularly in relation to the circadian rhythm. Researchers have shown that gut bacteria play a significant role in regulating the hypothalamic-pituitary-adrenal (HPA) axis, which controls the body’s reaction to stress.
The Connection Between Gut Microbiota and Stress
The stress and circadian systems, while serving different functions, are closely linked through the HPA axis and the autonomic nervous system. The stress response is designed to react quickly to threats, while circadian rhythms help the body anticipate environmental changes. One of the key hormones in both systems is glucocorticoid, which follows a daily pattern controlled by the brain’s central clock, the suprachiasmatic nucleus (SCN). This daily rhythm affects how the body handles stress, with greater resilience at certain times of the day.
Gut microbiota influences brain function through the HPA axis, impacting brain areas like the hippocampus and amygdala, which regulate stress. Disruptions to the microbiota can lead to irregular glucocorticoid levels, affecting stress responses and overall health.
About the Study
To investigate the role of gut microbiota in stress regulation, the researchers studied mice with depleted microbiota through antibiotic treatment (ABX) or germ-free (GF) conditions. Some mice received fecal microbiota transplantation (FMT) from either GF or ABX mice.
The mice were subjected to acute restraint stress, and the researchers measured blood glucose and corticosterone levels. Behavioral tests, such as reciprocal social interaction and open field tests, were also conducted to evaluate stress responses. Brain samples were analyzed for gene expression related to stress and circadian rhythms. Additionally, blood levels of corticosterone, adrenocorticotropic hormone (ACTH), and catecholamines were measured at different times of the day to assess circadian rhythms.
The study used advanced techniques such as shotgun sequencing of microbial DNA, RNA sequencing, and metabolomics to assess microbial and tissue responses. Data integration was performed using multi-omics analysis.
Key Findings
The study found that gut microbiota, particularly Lactobacillus species like Limosilactobacillus reuteri, plays a critical role in regulating daily fluctuations in corticosterone levels. In GF and ABX mice, the timing and intensity of corticosterone secretion were altered.
In GF mice, peak corticosterone levels shifted to the dark phase, while ABX mice had higher corticosterone levels at various times throughout the day, disrupting the body’s natural rhythm. These changes were mirrored in brain areas like the hypothalamus (SCN), hippocampus, and amygdala, which are essential for regulating circadian rhythms and stress.
Gene expression related to circadian rhythms and stress was altered in these regions, with some areas losing their natural rhythm. These disruptions were linked to changes in corticosterone release and may contribute to a higher risk of stress-related disorders like depression.
Gut microbial depletion also affected brain metabolism, particularly in pathways related to glutamate, a neurotransmitter crucial for stress responses. Changes in gene expression in the hypothalamus and pituitary gland reduced the permeability of the blood-brain barrier.
Behavioral changes were also observed. ABX mice exhibited less social interaction after stress, especially at certain times of the day. However, when corticosterone levels followed their normal patterns, these behavioral issues were alleviated. This finding was further confirmed by blocking corticosterone synthesis, which prevented stress-induced behavioral impairments.
Fecal microbiota transplants indicated that Lactobacillus reuteri specifically influences corticosterone levels, reinforcing the idea that certain gut bacteria play a role in regulating the stress response.
Conclusions
This study highlights the crucial role of gut microbiota in managing stress responses through its influence on circadian rhythms. Disruptions to the microbiota can lead to altered corticosterone release and changes in stress-related behaviors, which vary depending on the time of day.
The research suggests that further studies are needed to pinpoint specific microbial signals that regulate corticosterone rhythms, understand their impact on the brain, and apply these findings to human health, particularly for those with stress-related disorders.
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