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Gut microbiome-mediated activities of psychotropic drugs

Project description

Exploring interactions between psychotropic drugs and the gut microbiome

The gut microbiome, a collection of approximately 100 trillion microorganisms that colonise the gastrointestinal tract, play a critical role in nutrient extraction, metabolism and immunity. Recently, alterations in the gut microbiome have been linked to psychotropic medication use for treating mental illness. Given the varied and often ineffective responses of patients to these drugs, characterising the reciprocal interactions between them and gut microbes could lead to improved treatment for conditions including depression. The European Research Council-funded gutMAP project will tackle this challenge using synthetic and patient-derived microbe communities and in vivo gnotobiotic mouse models. Outcomes will inform microbiome-guided therapeutic strategies whose improved efficacy will be tested in vivo.

Objective

Mental illnesses are among the most prevalent health burdens, with major depression ranking fourth among the leading causes of disease worldwide. Although diverse psychotropic drugs are available, the delayed onset of drug action, high non-responder rates and frequent side effects still pose significant challenges. Several observations suggest the gut microbiome as major contributor to high inter-individual differences in drug responses. While there is evidence that these drugs lead to changes in the microbiome composition of patients, it has not yet been explored whether these effects are part of the drug mode of action and/or whether they contribute to side effects. The aim of this project is to investigate to what extent gut microbes are involved in the therapeutic outcome of psychotropic drugs by employing model synthetic and patient derived microbiome communities (from stool of drug responders, non-responders and healthy controls), and in vivo gnotobiotic mouse models. We will systematically characterize the reciprocal interactions between gut microbes and commonly used psychotropic drugs ex vivo – from microbial drug metabolism to drug-induced bacterial secretion of neuroactive compounds. For intriguing interactions, we will elucidate the underlying mechanisms and use the knowledge to design engineered microbiomes. We will then employ gnotobiotic knockout mice deficient for primary drug targets of psychotropic drugs and colonize them with microbiome communities carrying the different mapped traits to separate the contribution of drug effects originating from the microbiome from those of the host. Overall, our results will inform microbiome-guided therapeutic strategies whose improved efficacy we will test in vivo. Due to the transferability of the developed technology and if successful, this new research direction could not only revolutionize psychotropic drug therapy, but also pave new ways for improving personalized drug therapy for many other diseases.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-STG

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Host institution

EBERHARD KARLS UNIVERSITAET TUEBINGEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 497 033,75
Address
GESCHWISTER-SCHOLL-PLATZ
72074 Tuebingen
Germany

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Region
Baden-Württemberg Tübingen Tübingen, Landkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 497 033,75

Beneficiaries (1)

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