UCLA researchers have identified a novel high resilience brain gut microbiome phenotype and biological pathways by which stress related disorders may be prevented or reduced.
BACKGROUND: In the United States, stress-related health care costs and lost productivity exceed $300 billion annually, underscoring the urgent need to improve resilience: the ability to regain healthy and physiological function following adversity. Most existing research has examined resilience through psychological or social lenses, focusing on personality traits, emotional and behavioral regulation strategies, and social factors. However, no study to date has characterized an integrated biological profile of resilience that combines clinical phenotypes, microbiome function, and neural characteristics. Because strengthening resilience may prevent both mental and physical disease, there is a critical clinical need to define its comprehensive biological underpinnings.
INNOVATION: Researchers at UCLA have identified a high resilience (HR) brain gut microbiome (BGM) phenotype and uncovered potential biological pathways through which the onset and severity of stress-related psychiatric disorders might be prevented or attenuated. To characterize this phenotype, researchers collected (i) fecal samples for RNA and metabolomic profiling, (ii) physiological and cognitive questionnaires, and (iii) structural, functional, and diffusion magnetic resonance imaging (MRI) data. RNA and metabolomic profiling showed that HR individuals exhibited greater expression of bacterial transcripts involved in environmental adaptation, genetic propagation, energy metabolism, and anti-inflammatory pathways, alongside higher levels of N-acetylglutamate, a metabolite associated with gut integrity. Physiological and cognitive assessments suggested that the HR phenotype was associated with lower depression, anxiety, neuroticism, and perceived stress, alongside greater mindfulness, less judgment, and higher extroversion. MRI analyses demonstrated that HR was associated with enhanced connectivity between brain regions involved in reward and movement, as well as reduced gray and white matter volumes in areas responsible for emotion regulation. In summary, UCLA researchers have defined a multidimensional HR phenotype characterized by adaptive stress responses, improved gut-microbiome function, and neurological signatures supporting cognitive-emotional connections. These findings provide novel biological targets for therapeutics that enhance resilience.
POTENTIAL APPLICATIONS:
- Therapeutic target discovery (probiotics, diets, etc)
- Biomarker development
- Preventative health strategies
ADVANTAGES:
- First cross-disciplinary study to connect the gut and brain to resilience
- Noninvasive and scalable assessments
- High clinical translatability
- Provides biological evidence along with a self-reported questionary
DEVELOPMENT-TO-DATE: UCLA researchers have identified a novel high resilience brain gut microbiome phenotype and neurological signatures that support emotion regulation and cognitive-emotional connections through human observational data and ex vivo human samples.
Related Papers (from the inventors only):
An, E., Delgadillo, D.R., Yang, J. et al. Stress-resilience impacts psychological wellbeing as evidenced by brain–gut microbiome interactions. Nat. Mental Health 2, 935–950 (2024). https://doi.org/10.1038/s44220-024-00266-6
Keywords: Resilience, brain gut microbiome, RNA profiling, metabolic profiling, magnetic resonance imaging, N-acetylglutamate, cortical brain signatures