Major depressive disorder is one of the leading causes of disability and economic disparity. This is affecting approximately four out of ten people in the Netherlands at some point in their lives. Despite accumulated knowledge on depression, developing targeted treatment for the condition remains challenging. This is due to its multifactorial nature and heterogeneous clinical manifestations. The gut microbiome are bacteria residing in the gut that communicate with the brain. There is growing evidence supporting the involvement of gut microbiome in depressive disorders. This has become the theoretical foundation for the emergence of microbiome-based interventions as promising adjunctive alternatives. This project aims to identify microbial features (taxonomy, metabolic products) that can be developed as treatment strategies to potentially ‘beat’ depression. The project is a collaboration of Amsterdam UMC, Erasmus MC and SILS Amsterdam, funded by the ZonMw Open Competition 2024.

The project will leverage information derived from multiple large cohort studies (namely the Rotterdam Study and HELIUS). These studies are amounting to over 10,000 samples to perform a large-scale meta-analysis and identify candidate bacteria. Other omics data, such as metabolomics, will be coupled with microbiome information using sophisticated statistical analyses. Aiming to arrive at complex insights into cross-species interactions and the resulting metabolic products implicated in depressive symptoms. Combined with in vitro and in vivo validations, the project promises deeper insights into the complex mechanisms linking gut health and mental health, as well as prospective novel treatment candidates to alleviate depressive symptoms.