By Cara Michelle Miller
Your gut might be more than just a “gut feeling” when it comes to stress; it’s actually running on its own daily schedule to help you cope.
Gut bacteria—the ecosystem of tiny organisms inside of us—affect how well we handle stress, with their impact changing throughout the day, according to a new animal study.
The research showed that gut bacteria influence the stress response, which is linked to the body’s natural sleep-wake cycle. Disrupting gut bacteria in mice led to stress responses outside their normal circadian rhythm.
“The gut microbiome doesn’t just regulate digestion and metabolism; it plays a critical role in how we react to stress, and this regulation follows a precise circadian rhythm,” John Cryan, chair of the Department of Anatomy & Neuroscience at University College Cork in Ireland and principal investigator of the study, said in a press statement.
Our body’s internal clock, known as the circadian rhythm, helps control many functions, including sleep patterns and hormone levels. When these natural rhythms fall out of sync, it can lead to health problems, including mental health issues and mood disorders.
The new study, published Tuesday in Cell Metabolism, suggests that targeting gut bacteria could provide a way to treat disorders, such as depression and anxiety, often linked to disruptions in both our internal body clock and stress response system.
“This study is a significant leap forward in our understanding of how the microbiome shapes our mental health,” professor Paul Ross, director of APC Microbiome Ireland, stated in another press release.
How Gut Bacteria Regulate Stress
The study, conducted in mice, shows that gut bacteria imbalances can disrupt the body’s internal clock, triggering changes in stress responses that may contribute to mental health conditions.
Researchers found that when gut bacteria were depleted—either by giving antibiotics to regular mice to reduce gut bacteria or by using germ-free mice with no gut bacteria—stress responses became overactive at specific times of the day. This overactivity was linked to disruptions in the brain regions that control stress and circadian rhythms, leading to abnormal stress reactions, changes in hormone levels, and anxiety-like behavior in the mice.
A fundamental discovery involved the bacteria Limosilactobacillus reuteri (L. reuteri). This beneficial bacteria, commonly used in probiotics, fluctuates in abundance throughout the day. These fluctuations were linked to the release of stress hormones.
This points to gut bacteria’s broader role in regulating not just digestion, but also stress and circadian rhythms, according to the researchers.
Disruptions in Stress Hormones
The research team focused on corticosterone, a stress hormone in mice similar to human cortisol. Corticosterone levels naturally rise and fall throughout the day as part of the body’s stress response. For example, corticosterone peaks in the early morning as the body prepares for the day.
However, disrupting the gut microbiome threw off this natural pattern.
In mice without gut bacteria, corticosterone’s usual daytime peak shifted to nighttime. This shift could impair the body’s ability to handle stress at the right times, potentially contributing to chronic stress and anxiety.
In antibiotic-treated mice, the hormone’s peak was more pronounced than normal and occurred at the wrong time of day—during the “lights out” period, when the body’s circadian system signals to rest. These misaligned hormone releases could lead to stress overload, as hormones are released when the body is unprepared for them.
The findings suggest that an imbalanced gut microbiota may upset the timing of our stress response, further disrupting our internal clock, according to the researchers.
“These findings underscore the importance of maintaining a healthy microbiome, particularly for those living in today’s stressful and fast-paced environment,” added Cryan, who is also a professor of anatomy at University College Cork.
The Brain and Circadian Disruptions
In addition to hormonal changes, the researchers found that gut microbiota imbalances affected brain regions involved in both stress regulation and circadian rhythms, including the limbic system: the hypothalamus, amygdala, and hippocampus. These areas control how we react to stress.
“By showing that gut bacteria influence how the body handles stress throughout the day, we’re helping to understand the mechanisms through which the microbiota shapes our responses to the environment around us,” said first study author Gabriel Tofani, highlighting the therapeutic potential of their findings.
Stress responses are not just about the intensity of the stress, but also about when and how the body reacts to it. According to the researchers, this makes timing stress-hormone patterns crucial for developing therapies that could restore balance to our stress response system, potentially improving mental health by aligning treatment with our natural circadian rhythm.
Future of Microbes in Therapy
This discovery opens up possibilities for improving mental health through psychobiotics—microbial-based therapies that use gut bacteria and other microorganisms to restore balance to the gut and the stress response system.
In recent years, self-reported stress has increased. According to the American Psychological Association:
- In 2020, nearly half of all U.S. adults (49 percent) said stress negatively affected their behavior.
- In 2022, over three-quarters of adults reported symptoms of stress, including headache, tiredness, and depression.
- In 2024, 43 percent of adults reported feeling more anxious than the year before.
This growing stress is closely linked to mental health challenges. As of October 2023, about 33 percent of women and about 24 percent of men reported anxiety symptoms. At the same time, about 23 percent of women and almost 22 percent of men reported symptoms of depression, according to USAFacts.
Considering the prevalence of anxiety and depression, the researchers said they believe that psychobiotics could help people better manage stress-related health conditions. In particular, L. reuteri could become a target for treatments aimed at restoring healthy circadian rhythm and boosting resilience to stress.
“The potential to improve mental health through microbiome-based interventions is very real,” said Ross, “and this study takes us one step closer to that goal.”
