Background: The brain gut-microbiome system is intricately connected to the psychological stress response. Decades of established research shows that stress is a risk factor for numerous detrimental health outcomes including cardiovascular disease, sudden heart attack, Irritable Bowel Syndrome, and gut dysbiosis. Indeed, upwards of $300 billion dollars is lost annually due to stress-related health care costs and missed work in the U.S., highlighting a vital need for greater resilience to stress.
Aims: The current work tests the hypothesis that there is a multi-omic (clinical; psychological, neurological, and gut microbiome) signature differentiating high from low stress-resilient groups.
Methods: Hypotheses were tested using data from 116 healthy adults (61% female, mean age=32.5 years). High/low stress-resilient groups were identified using the Connor-Davidson Resilience Scale (CD-RISC; a commonly used, validated, self-report scale measuring individuals resilience to stress). Multimodal fMRI were used to assess neurological features and functions. Microbial functions were assessed using transcriptomics and metabolomics. Data integration analysis using latent components (DIABLO) was used to discover whether psychological, neurological, microbiome and metabolome features distinguished high from low resilience phenotypes. A complete list of all DIABLO selected psychological, neurological, and microbial variables included in the model are depicted in Figure 1.
Results: DIABLO analyses showed that the high resilience group showed lower levels of depression and anxiety, higher frequency of bacterial transcriptomes (related to environmental adaptation, genetic propagation, energy metabolism, anti-inflammation), increased metabolites (N-acetylglutamate; dimethylglycine), and cortical signatures (increased resting state functional connectivity between reward circuits and sensorimotor networks; decreased grey matter volume and white matter tracts within the emotion regulation network; see Figure 1). Our findings support a multi-omic signature involving the BGM system suggesting that resilience impacts psychological symptoms, emotion regulation and cognitive function as reflected by unique neural correlates and microbiome function supporting eubiosis and gut barrier integrity. Bacterial transcriptomes provided the highest classification accuracy (see Figure 2).
Conclusion: Our findings suggest that the microbiome is critical in shaping resilience and highlights that microbiome modifications have the potential to increase resilience to psychological stress.

Madelaine Leitman

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