A pioneering study has uncovered the vital role that gut microbiota plays in regulating stress responses by interacting with the body’s circadian rhythms.

Published in Cell Metabolism, the study examined the intricate relationship between the gut microbiota and the hypothalamic-pituitary-adrenal (HPA) axis, the body’s central stress response system. The research demonstrated that depletion of gut microbiota leads to an hyperactivation of the HPA-axis in a time-of-day specific manner, which alongside with alterations to the brain’s stress and circadian responding regions, results in altered stress responsivity across the day.

According to the researchers from University College Cork and APC Microbiome Ireland, a Research Ireland Centre, the findings offer compelling evidence that the trillions of micro-organisms in the gut orchestrate the body’s hormonal responses to stress in a time-dependent manner, paving the way for new therapeutic approaches targeting the gut-brain axis.

Key findings included:

• That the gut microbiome regulates the body’s diurnal (day-night) rhythms in stress hormones

• Depletion of gut microbiota results in disruptions in the brain’s core circadian system, and is associated with altered stress hormone rhythms

• The research highlights that gut microbes also regulates key stress-responding brain regions throughout the day.

• Using microbe transplantation, the team confirmed that oscillations of gut microbes across the day are critical for regulating stress hormone secretion.

The study further identified specific gut bacteria, including a Lactobacillus strain (Limosilactobacillus reuteri), as key influencers of this circadian-regulated stress mechanism. L. reuteri emerged as a candidate strain that modulates glucocorticoid secretion (stress hormones), linking the microbiota’s natural diurnal oscillations with altered stress responsiveness.

The researchers believe that developing new microbial-based therapies that target gut bacteria could help individuals better manage stress related mental health conditions, such as anxiety and depression, which are often associated with alterations in circadian and sleep cycles.

Speaking about the findings, first author Dr Gabriel Tofani said that their findings underscored the importance not only of the gut microbiota composition, but also how gut microbes change across the day. 

“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. Our work also demonstrates that exploring this relationship between the gut microbiota and circadian rhythms will be key in the development of microbiota based therapies for the stress-related disorders in the future”.