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KFO 5024:  Immune checkpoints of gut to brain communication in inflammatory and neurodegenerative diseases (GB.Com)

Subject Area Medicine
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 505539112
 
The gut-brain axis is a bidirectional communication system driven by neural, hormonal, metabolic, immunological, and microbial signals. Signaling events from the gut can modulate brain function and recent evidence suggests that a dysregulated gut-brain axis plays a pivotal role in linking gastrointestinal and neurological diseases. In this context, clinical data reveal that patients with Inflammatory Bowel Disease (IBD) are at higher risk of subsequently developing Parkinson's disease (PD). In addition, the association between Multiple Sclerosis (MS) and IBD has been suggested, apart from their common epidemiological and immunological patterns, also due to observations of increased incidence of both IBD among MS patients and MS among IBD patients. Accordingly, a bidirectional link between gastrointestinal inflammation and neurodegeneration/ neuroinflammation, in accordance with the idea of the ‘gut–brain axis’, has recently emerged. In particular, enteric dysbiosis, translocation of bacterial products as well as inflammatory cells/soluble factors derived from the inflamed intestinal mucosa across the gut epithelial- and blood-brain-barrier (BBB) have been implicated as major factors for structural and functional alterations in the CNS. While the concept of a pathophysiological gut-brain axis is increasingly recognized, in-depth characterization of inter-organ communication to identify immunological checkpoints that control this network during health and disease, is limited. The overall aim of this clinical research unit is to delineate the interactions between the intestinal and the nervous system across the gut-brain axis in the context of immune-mediated inflammatory and degenerative diseases. Cross-fertilization between the research foci immunology and neuroscience will allow us to gain unique new insights into the pathogenesis of these disorders to establish the necessary scientific foundation for the future development of novel diagnostic and therapeutic tools. Controlling the disease activity in one of the organs may reduce the risk of developing inflammation/degeneration in the other direction of the axis, potentially owing to a reduction in disease activity and modulation of the gut-brain axis. To reach this goal, we will combine our strong expertise in basic and clinical neuroimmunology, neurodegeneration, gastroenterology, and mucosal immunology. Using a strictly interdisciplinary approach, we aim for the replacement of the traditionally organ centered perception of inflammation. In the long-term perspective, we aim to obtain a comprehensive understanding of gut-brain communication for the identification of novel biomarkers, therapeutic targets, interventional strategies and predictors of treatment response to improve patient care.
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