ProbioBrain
PROJECT DURATION:
10/2024
—
09/2025
The Project
Due to the communication between the gut and brain, the gut microbiome is increasingly associated with mental illnesses such as depression and there is great potential for therapeutic interventions in this way. It has already been shown that depressive behavior in mice improved after probiotic administration and that the expression of genes involved in a metabolic pathway potentially relevant to depression was altered. The aim of the ProbioBrain project is to investigate the effect of the probiotics Enterococcus mundtii and Geotrichum candidumin direkt im Gehirn auf Stoffwechselwege im Mausmodell zu untersuchen.
Our Role in the Project
The technology of open cerebral microperfusion (cOFM) was developed at the HEALTH Institute to measure the transport of substances from the bloodstream across the intact blood-brain barrier into the brain. As part of the ProbioBrain project, metabolic pathway changes via the gut-brain axis are analyzed directly in the brain. The samples obtained are analyzed and evaluated at the HEALTH Institute.
Research groups
Downloads
Customer/Funding Organization
Land Steiermark
Project Partner
Priv.-Doz. Dr. Aitak Farzi am Otto Loewi Forschungszentrum (Medizinische Universität Graz)
Dr. Muhammad Imran Professor und Provost an der Fakultät für Biowissenschaften (Quaid-i-Azam-Universität Islamabad Pakistan)
Project Details
Currently, around 5% of all people worldwide (that's around 350 million people) are diagnosed with depression, and as pharmacological interventions are currently suboptimal, the burden of depression and its effects on the healthcare system is enormous. Due to bidirectional communication via the gut-brain axis, the gut microbiome is increasingly associated with depression and therapeutic interventions through this pathway have great potential. Studies in mouse models have already shown that oral administration of probiotics can improve depressive behavior and after administration of probiotics, the expression of genes involved in tryptophan kynurenine metabolism was shown to be altered. This metabolic pathway could play an important role in depression, as it regulates inflammatory reactions, which are often associated with depression. In the mouse model, modifications in the intestinal microbiome also occurred after the administration of probiotics, which indicate changes in tryptophan metabolism. However, the direct effects of probiotics on metabolic pathways in the brain are still largely unexplored.
The aim of the ProbioBrain project is to investigate the changes in metabolic pathways and in particular those of the tryptophan-kynurenine metabolic pathway directly in the brain in a mouse model after oral administration of the probiotics Enterococcus munditii and Geotrichum candidumin. This is possible for the first time using the innovative cerebral OFM sampling technology in combination with metabolomic analyses.
To achieve this goal, the probiotics Enterococcus munditii and Geotrichum candidum are administered. The animals are maintained under chronic mild stress conditions (stress model) or in standard maintenance (control model). Interstitial fluid (ISF) is sampled directly from the brain using the innovative sampling technology cerebral open microperfusion (OFM) and samples are subjected to metabolic analysis. The metabolites present in the ISF samples are analyzed with a focus on changes in metabolic pathways in the brain, in particular the tryptophan-kynurenine pathway.
The results of these analyses can make a decisive contribution to understanding the mechanisms triggered by probiotics via the gut-brain axis in the brain and therefore have the potential to have a lasting impact on therapeutic approaches to the treatment of depression.
