Stress has a profound impact on our lives, contributing to a staggering $300 billion in healthcare costs and missed workdays in the United States alone each year. The way we handle stress, known as resilience, can make a significant difference in how we navigate life’s challenges. Now, new research from the University of California, Los Angeles (UCLA) has provided groundbreaking insights into the biology of resilience, revealing that it involves not only the brain but also the gut microbiome, the vast community of microorganisms that live in our digestive tract.
The study, published in Nature Mental Health, found that people who exhibit greater resilience tend to have more activity in brain regions associated with better cognitive functioning and emotional regulation. These resilient individuals were also more mindful, better at describing their feelings, and had different gut microbiome activity compared to those who were less resilient. This connection between the brain and the gut microbiome could pave the way for new interventions to help people manage stress more effectively.
The research team at UCLA was motivated by the increasing evidence linking stress with mental health issues like depression and anxiety. While previous studies have shown that resilience can protect against these conditions, most of the research has focused on psychological traits and social factors. The UCLA researchers wanted to take a different approach by exploring the biological underpinnings of resilience.
By identifying what a “resilient” brain and microbiome look like, the researchers hoped to open up new avenues for treatments that could enhance resilience and reduce the risk of stress-related mental health disorders. According to Arpana Church, the senior author of the study and co-director of the UCLA Goodman-Luskin Microbiome Center, the ultimate goal is to develop targeted interventions that can help people better cope with stress by focusing on both the brain and the gut.
“We often focus our energy on investigating disease and treating disease. Or even how stress leads to disease,” Church told PsyPost. “But I wanted to know what if we flipped the switch and looked at the other side of the coin, by investigating those individuals who despite experiencing stress do well and do not develop disease? I strongly believe that by pursuing this line of investigation we can think about preventing disease before it even begins.”
The study involved 116 healthy adults from the Los Angeles area. To assess resilience, the researchers used the Connor-Davidson Resilience Scale, a well-validated self-report questionnaire. This scale asks participants to rate how true certain statements are for them, such as “I can handle unpleasant feelings” or “I tend to bounce back quickly after hard times.” Based on their scores, participants were divided into two groups: those with high resilience and those with low resilience.
The participants underwent several types of brain imaging to capture different aspects of brain structure and function. These included high-resolution structural MRI scans to measure the volume and surface area of different brain regions, diffusion MRI to assess the connectivity between brain regions by examining the white matter tracts, and resting-state functional MRI to observe how different regions of the brain communicate with each other when the brain is at rest.
In addition to the brain imaging, participants provided stool samples a few days before their MRI scans. These samples were used to analyze the gut microbiome, focusing on both its composition (which microorganisms are present) and its function (what genes are active and what metabolites are being produced). The stool samples were processed to extract DNA and RNA, allowing the researchers to examine the genetic activity of the microbiome and identify specific microbial functions related to resilience.
In addition to resilience, the study measured several other psychological and behavioral traits using standardized questionnaires. These included measures of anxiety, depression, mindfulness, cognitive abilities (such as memory and attention), and perceived stress. By examining these traits alongside the biological data, the researchers aimed to identify correlations that could shed light on the mechanisms underlying resilience.
The brain imaging data revealed that individuals with high resilience showed greater activity in brain regions associated with emotional regulation and cognitive functioning. Specifically, they had more activity in the anterior cingulate cortex and prefrontal cortex. These regions help control the “fight or flight” response, preventing it from becoming overwhelming and allowing for more adaptive responses to stress.
Moreover, the high-resilience group exhibited different patterns of brain connectivity. They showed stronger connections within the brain’s default mode network (DMN), which is involved in self-referential thinking and daydreaming, but also plays a role in recovering from stress. The DMN’s connections with other brain regions, such as those involved in emotional processing and the brainstem, were more robust in the high-resilience group. This suggests that resilient individuals may have a more coordinated brain network that helps them manage stress more effectively.
The analysis of the gut microbiome revealed significant differences between the high-resilience and low-resilience groups. The microbiomes of the high-resilience group were more likely to produce metabolites that reduce inflammation and strengthen the gut barrier. These metabolites, such as short-chain fatty acids, are known to have anti-inflammatory properties and play a crucial role in maintaining the integrity of the gut barrier—a critical factor in preventing harmful substances from entering the bloodstream and triggering systemic inflammation.
Additionally, the high-resilience group had a gut microbiome that exhibited increased activity in genes related to environmental adaptation, genetic propagation, and metabolism. These findings suggest that a resilient individual’s microbiome is better equipped to handle changes and stressors, potentially contributing to their overall ability to cope with stress. The researchers also noted that the high-resilience group’s microbiome was associated with better gut health, as indicated by the production of metabolites that support a strong and healthy gut barrier.
One of the key strengths of this study is how it integrated the brain and gut data to provide a comprehensive picture of resilience. By using advanced statistical techniques, the researchers were able to identify specific patterns of brain activity, brain structure, and gut microbiome function that distinguished the high-resilience group from the low-resilience group.
For example, they found that certain brain regions’ connectivity patterns were linked to specific gut microbiome activities. This supports the idea of a bidirectional relationship between the brain and the gut, where the gut microbiome can influence brain function and vice versa. The study’s findings suggest that resilience is not just a psychological trait but also a biological one, involving a complex interaction between the brain and gut microbiome.
The study also found that the high-resilience group scored better on several psychological measures. They were less likely to experience anxiety and depression, scored higher on measures of mindfulness, and performed better on cognitive tasks related to memory and attention. These psychological traits were correlated with the biological markers identified in the study, further reinforcing the idea that resilience is a multifaceted phenomenon involving both the mind and body.
“Resilience truly is a whole-body phenomenon that not only affects your brain but also your microbiome and what metabolites that it is producing,” Church said. “When you’re stressed, your brain sends signals to your gut. This can upset the balance of your gut bacteria, leading to digestive issues like stomachaches or changes in your bowel movements. But it goes beyond that—the gut bacteria also send signals back to your brain, which can make you feel more anxious or stressed, creating a loop.”
“This connection is why managing stress is so important. If you’re constantly stressed, it can keep this cycle going, leading to chronic inflammation, weakening your immune system, and increasing your risk of long-term illnesses like heart disease, diabetes, and even mental health conditions like depression. By managing stress, you help maintain a healthy balance in your gut, which in turn supports your overall physical and mental well-being.”
Despite the groundbreaking nature of the study, the researchers acknowledge some limitations. One major limitation is that the study was cross-sectional, meaning it looked at a single point in time rather than following participants over time. This makes it difficult to determine whether the brain and gut differences observed in the study cause resilience or are a result of it. Future studies will need to take a longitudinal approach, tracking changes in resilience, brain function, and gut microbiome activity over time to better understand these relationships.
Another limitation is the study’s focus on healthy adults. While this was important for establishing a baseline understanding of resilience, future research should also include people with mental health conditions like depression and post-traumatic stress disorder. Comparing these groups could help identify how the brain and gut microbiome might differ in individuals who struggle with resilience.
Looking ahead, the researchers are excited about the potential for developing new treatments based on their findings. By targeting both the brain and the gut, it may be possible to create interventions that enhance resilience and prevent mental health conditions before they start. This could include dietary changes, probiotics, or even more advanced therapies like fecal transplants.
“Resilience truly is a whole-body phenomenon,” Church said. “We have this whole community of microbes in our gut that exudes therapeutic properties and biochemicals, so I’m looking forward to building upon this research.” The team plans to explore whether interventions designed to increase resilience can change both brain and gut microbiome activity, potentially offering a new way to boost mental health and well-being.
“While we wait for the development of targeted resilience treatments, eating diets rich in diverse fruits and vegetables is the best way to support a healthy gut microbiome and intern healthy brain,” Church explained. “I talk about the ‘ABC’s’ (always be counting), if we can count and get 30 different vegetables and fruits per week we will be helping maintain a healthy microbiome. Therefore, by making mindful dietary choices, we can help maintain a healthy gut microbiome and support optimal brain function and mental well-being.”
The study, “Stress-resilience impacts psychological wellbeing as evidenced by brain–gut microbiome interactions,” was authored by Eric An, Desiree R. Delgadillo, Jennifer Yang, Rishabh Agarwal, Jennifer S. Labus, Shrey Pawar, Madelaine Leitman, Lisa A. Kilpatrick, Ravi R. Bhatt, Priten Vora, Allison Vaughan, Tien S. Dong, and Arpana Gupta (Church).
