Stress resilience – state of mind or state of gut?
Over the last three decades, stress has been increasingly considered a risk factor with a predetermined detrimental outcome. Stress induces a whole range of phenotypes with stress resilience at one end of the spectrum and susceptibility at the other. The project DE-STRESS has identified possible signatures of stress resilience which could form the basis for the development of future treatment of stress-induced psychopathologies. “Specifically, we focused on the impact on the neuroendocrine and immune systems, synaptic plasticity, gene expression in the brain and the gut microbiome,” explains Dr Anand Gururajan, the Marie Skłodowska-Curie Action (MSCA) fellow who led the DE-STRESS project. Chilled-out mice have different molecular signatures compared to those feeling the pressure DE-STRESS researchers used several different techniques to analyse mice which were classified as resilient or susceptible to social stress. Susceptible mice had a notably different hormonal signature to their relaxed counterparts. In particular, they had higher peripheral levels of the stress hormone, corticosterone (cortisol in humans), and also had heavier adrenal glands; this is the organ that releases corticosterone into the periphery. Moreover, expression of corticotropin release factor (Crf) gene from the prefrontal cortex of susceptible mice was higher. This is a gene that mediates the release of corticosterone. “Our most surprising finding was that microbiome composition at baseline seemed to co-vary with several post-stress response outcomes. The significance of this finding is high as analysis of the microbiome at baseline could predict how an organism will respond to stress,” emphasises Dr Gururajan. Research hurdles and their solutions Data analysis was delayed and had to be repeated due to the host institution’s lengthy tendering process. “For one of our work packages, we decided to use the latest in gene editing technologies, CRISPR. Breeding the CRISPR mice to sufficient numbers before they could be used for experimental purposes proved time consuming,” explains Dr Gururajan. There was also a significant delay in obtaining the necessary viruses to edit the Crf gene in vivo. Luckily, project planning had included contingency time when Dr Gururajan analysed data from earlier packages, wrote manuscripts and prepared all-important presentations for conferences. Planned stress-busting with the microbiome DE-STRESS results indicate that treating stress-induced psychopathologies or inducing resilience to stress via the gut microbiome is an exciting and practical approach. One of the main follow-up investigations has been to identify specific psychobiotic formulations which are beneficial in this context. “This,” Dr Gururajan points out, “could lead to promising collaborative and commercialisation opportunities with industry partners.” From the perspective of an MSCA fellow, he concludes: “I’ve been able to carry out this highly topical research project and generate data for up to three original research papers. The fellowship has allowed me to attend several conferences in Europe and the United States and to secure funding as a research fellow at the University of Sydney, Australia. Further EU funding for this programme in particular would improve the lives of sufferers of depression worldwide.”
Keywords
DE-STRESS, microbiome, resilience, corticosterone, depression, susceptibility, Crf, corticotropin release factor, adrenal gland
