Kidney disease reprograms microbiome-host signaling to promote heart failure

Yarritu, Alex; Anders, Wibke; Thiele, Arne; Potapenko, Olena; Schumacher, Fabian; Szijártó, István A.; Matz-Rauch, Ariana; Versnjak, Jakob; Gebremedhin, Natnael; McParland, Victoria; Heckscher, Simon; Kamboj, Sakshi; Trimarchi, Giuseppe; Anandakumar, Harithaa; Fuckert, Franziska; Hoffmann, Carina; Hassan, Sara A.; Bonnekoh, Paul M.; Wimmer, Moritz I.; Behrens, Felix; Voelkl, Jakob; Kramann, Rafael; Kintscher, Ulrich; Kuehne, Titus; Kleuser, Burkhard; Zernecke, Alma; Oefner, Peter J.; Gronwald, Wolfram; Dettmer, Katja; Eckardt, Kai-Uwe; Müller, Dominik N.; Kelm, Marcus; Holle, Johannes; Bartolomaeus, Hendrik; Wilck, Nicola

Kidney disease reprograms microbiome-host signaling to promote heart failure

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Item Type:	Preprint
Title:	Kidney disease reprograms microbiome-host signaling to promote heart failure
Creators Name:	Yarritu, Alex, Anders, Wibke, Thiele, Arne, Potapenko, Olena, Schumacher, Fabian, Szijártó, István A., Matz-Rauch, Ariana, Versnjak, Jakob, Gebremedhin, Natnael, McParland, Victoria, Heckscher, Simon, Kamboj, Sakshi, Trimarchi, Giuseppe, Anandakumar, Harithaa, Fuckert, Franziska, Hoffmann, Carina, Hassan, Sara A., Bonnekoh, Paul M., Wimmer, Moritz I., Behrens, Felix, Voelkl, Jakob, Kramann, Rafael, Kintscher, Ulrich, Kuehne, Titus, Kleuser, Burkhard, Zernecke, Alma, Oefner, Peter J., Gronwald, Wolfram, Dettmer, Katja, Eckardt, Kai-Uwe, Müller, Dominik N., Kelm, Marcus, Holle, Johannes, Bartolomaeus, Hendrik and Wilck, Nicola
Abstract:	Gut microbiome-derived metabolites regulate host physiology, with systemic levels controlled by renal excretion. In kidney disease, impaired clearance leads to metabolite accumulation, inflammation, and secondary cardiovascular damage. We show that adverse cardiac remodeling following kidney disease critically depends on the microbiome. We identify microbiome-derived indoxyl sulfate-mediated activation of the aryl hydrocarbon receptor (AhR) as a key mechanism promoting IL-17A-producing T cells and cardiac fibrosis. AhR inhibition attenuates inflammation and cardiac remodeling. On population level, IL-17A is elevated in chronic kidney disease, particularly with coexisting heart failure. Mechanistically, AhR and IL-17A signaling induce a pro-fibrotic phenotype in cardiac fibroblasts, with conserved responses in human cells. This work identifies a microbiome-AhR-IL-17A axis as a mediator and druggable target of cardiovascular damage in kidney disease.
Keywords:	Animals, Mice
Source:	bioRxiv
Publisher:	Cold Spring Harbor Laboratory Press
Article Number:	2026.01.10.698142
Date:	12 January 2026
Official Publication:	https://doi.org/10.64898/2026.01.10.698142

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