The composition and function of the microbiome have been linked to stress-related disorders and other mental health diagnoses. The results of a human study headed by researchers at UCLA have found that resilient people exhibited neural activity in the brain regions associated with improved cognition and regulating of emotions, and were more mindful and better at describing their feelings. The same group of people also exhibited gut microbiome activity linked to a healthy gut, with reduced inflammation and strong gut barrier.

To conduct the study, the researchers surveyed 116 people about their resiliency—like trust in one’s instincts and positive acceptance of change—and separated them into two groups. One group ranked high on the resiliency scale and the other group ranked low. The participants also underwent MRI imaging and gave stool samples two or three days before their scans.

This is believed to be the first study to explore the intersection of resiliency, the brain, and the gut microbiome. “If we can identify what a healthy resilient brain and microbiome look like, then we can develop targeted interventions to those areas to reduce stress,” said Arpana Gupta, PhD, co-director of the UCLA Goodman-Luskin Microbiome Center. Gupta is senior author of the team’s published paper in Nature Mental Health, titled “Stress-resilience impacts psychological well-being as evidenced by brain–gut microbiome interactions.” In their paper, the team concluded, “This study has identified a high-resilience phenotype of the brain–gut microbiome system and reveals promising pathways by which the onset and severity of stress-related psychiatric conditions might be prevented or mitigated.”

The authors cited figures indicating that more than $300 billion is lost annually due to stress-related healthcare costs and missed work in the United States, “… highlighting the need for greater resilience to stress,” they wrote. Definitions of resilience may refer to beneficial outcomes in response to threat or stressful events. “Resilience can predict stress-related depression and anxiety traumatic stress and maladaptive coping mechanisms such as alcohol misuse.”

The brain–gut microbiome (BGM) system plays an influential role on mental health, they noted, with multiple animal studies revealing the role of BGM in resilience versus susceptibility traits after exposure to stress. Such results, they suggested, point to “… the intriguing possibility that the endogenous gut microbiome may house stress-mitigating therapeutic metabolites supporting neurologically adaptive processes.”

For the study, rather than examine microbiome activity and composition linked to disease conditions—such as anxiety and depression—the researchers wanted to flip the script and study the gut microbiome and brain in healthy, resilient people who effectively cope with different types of stress, including discrimination and social isolation.

Gupta and colleagues aimed to determine how resilience is related to clinical phenomes, microbiome function, and neural characteristics. They focused on methods to cope with stress because research has shown that untreated stress can increase the risk of heart disease, stroke, obesity, and diabetes. While stress is an inevitable part of life, studying how to handle stress can help prevent developing diseases.

The researchers found that people in the high resiliency (HR) group were less anxious and depressed, less prone to judge, and had activity in regions of the brain associated with emotional regulation and better cognition compared to the group with low resiliency (LR). “When a stressor happens, often we go to this aroused fight or flight response, and this impairs the breaks in your brain,” Gupta said. “But the highly resilient individuals in the study were found to be better at regulating their emotions, less likely to catastrophize, and keep a level head,” added Desiree Delgadillo, PhD, a postdoctoral researcher and one of the first authors.

The high resiliency group also had different microbiome activity than the low resiliency group. Namely, the high resiliency group’s microbiomes excreted metabolites and exhibited gene activity associated with low inflammation and a strong and healthy gut barrier. A weak gut barrier, otherwise known as a leaky gut, is caused by inflammation and impairs the gut barrier’s ability to absorb essential nutrients needed by the body while blocking toxins from entering the gut. “…  our findings suggest resilient individuals, particularly those demonstrating tenacity and perceived ability to control life outcomes, possess a microbiome that supports gut-barrier integrity and eubiosis and a cortical signature that reflects adaptive emotional and cognitive regulation,” the team stated.

The researchers were surprised to find these microbiome signatures associated with the high resiliency group. “Resilience truly is a whole-body phenomenon that not only affects your brain but also your microbiome and what metabolites that it is producing,” Gupta said. Delgadillo added, “We have this whole community of microbes in our gut that exudes these therapeutic properties and biochemicals, so I’m looking forward to building upon this research.” As the investigators commented, “Our findings show that the HR group may host a gut microbiome that can withstand perturbations, as evidenced by an increase in metabolites that quell inflammation, which, in turn, may support optimal neurological processes.”

The team’s future research will study whether an intervention to increase resilience will change brain and gut microbiome activity. “We could have treatments that target both the brain and the gut that can maybe one day prevent disease,” Gupta said. In their paper, Gupta and colleagues further noted, “Some clinical implications to explore are whether dietary modifications, prebiotics, probiotics, or other clinical interventions (for example, fecal transplantation) may improve coping and resilience to stress.”

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