European Commission logo
English English
CORDIS - EU research results
CORDIS

Parkinson's disease: does it all start with gut inflammation?

Project description

Gut inflammation and the origin of Parkinson's disease

Growing evidence shows that Parkinson's disease (PD) involves the gut before affecting the brain, leading to the fascinating hypothesis that the gut might be the site of disease initiation. The theory that PD originates from an inflammatory insult in the gut is supported by the observation that PD-relevant genetic traits also modulate immune responses to enteric pathogens and confer risk to gut inflammation. The EU-funded PD-GUT project aims to decode the role of intestinal inflammation in PD and to identify mediators of immune cell contributions to neurodegeneration, using patient stem cell-derived organoids, organ-on-a-chip and single-cell sequencing technologies.

Objective

Burgeoning evidence shows that Parkinson's disease (PD) involves the gut before affecting the brain, leading to the fascinating hypothesis that the gut might be the site of disease initiation. Remarkably, the gut origin of PD is still poorly understood. Multiple triggers could serve as a first insult: infections, dysbiosis, and inflammatory bowel diseases (IBDs). All these conditions ultimately converge on intestinal inflammation. Thus, an intriguing hypothesis is that PD is a systemic illness that originates from an inflammatory insult in the gut. This hypothesis is based on the observation that genetic traits relevant for both sporadic and familial PD also modulate immune responses to enteric pathogens and confer risk to IBDs. To dissect shared mechanisms among these seemingly unrelated diseases, I envision a multi- and interdisciplinary project with a unique integration of competences in neuroscience, immunology, and microbiology. Moving beyond the state of the art, I will combine patient stem cell-derived organoid, organ-on-a-chip, and single-cell sequencing approaches to decode the role of intestinal inflammation in PD and to identify new mediators of immune cell contributions to neurodegeneration. Specifically, I will i) mechanistically dissect cell type-specific host immune responses to intestinal pathogens and their link to PD; ii) establish complex human pluripotent stem cell-derived intestinal organoids to investigate intestinal inflammation; and ii) implement patient multiorganoid platforms to identify key players in the communication between the inflamed gut and the brain. Unveiling the critical steps that initiate PD may lead to a conceptual leap forward in our understanding of how the gut affects the brain in both health and disease. The novel methodologies that will be developed will also lay the foundations for future interventions aimed at targeting intestinal inflammation in enteric and neurological diseases.

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 1 999 722,50
Address
RUE DE TOLBIAC 101
75654 Paris
France

See on map

Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 1 999 722,50

Beneficiaries (2)