Cabreiro, Filipe | Struble, Sebastian | Solagna, Francesca - C 04

Primary cilia are microtubule-based organelles critical for cellular signalling, and their dysfunction leads to ciliopathies, including polycystic kidney disease (PKD). PKD is characterized by renal cyst growth, driven by metabolic reprogramming, mitochondrial dysfunction, and altered cellular signalling. Emerging evidence suggests that the gut microbiome influences PKD progression through microbial metabolites such as short chain fatty acids (SCFAs) and uremic toxins, modulating inflammation and fibrosis. 

However, whether gut dysbiosis is a cause or consequence of PKD remains unclear. This project investigates the gut-kidney axis in PKD using germ-free and conventionally raised JCK mice, a model of genetic PKD, to dissect how microbial metabolites impact disease progression. We will identify key microbial-derived metabolites that influence renal function and test their therapeutic potential using gnotobiotic colonization strategies. 

Additionally, we will leverage a human biobank from the KETO-ADPKD trial (NCT04680780) and DILKID-Trial (NCT05709600) to validate findings in dietary interventions (ketogenic, caloric restriction, and sulfur amino acid-deficient diets). By integrating multi-omics approaches—metagenomics, metabolomics, and proteomics—we aim to uncover novel microbiome-mediated mechanisms in PKD and identify biomarkers for therapeutic targeting. Our findings could lead to microbiome-based interventions to slow PKD progression.

PKD lacks curative treatments, with tolvaptan only slowing disease progression. Our research explores the gut-kidney axis as a novel therapeutic target, leveraging microbial metabolites to modulate disease pathways. By identifying microbiome-derived biomarkers and dietary interventions, we aim to develop sustainable, non-pharmacological strategies to improve renal resilience. These insights could transform PKD management, offering personalized nutrition and microbiome-modulating therapies to delay kidney failure.

For more information, please check the Cabreiro Lab. 

• Center for Molecular Medicine Cologne (CMMC)
• CECAD
• MRC London Institute of Medical Sciences
• Institute for Genetics
• Cologne Graduate School

• Center for Molecular Medicine Cologne (CMMC)

• Center for Molecular Medicine Cologne (CMMC)
• CECAD
• Institute for Genetics