Inulin gel-mediated delivery of Clostridium butyricum spores protects against acute kidney injury via GPR43-GRP75 axis-regulated ER-mitochondria contact

ABSTRACT: Introduction: Acute kidney injury (AKI) is linked to gut microbiota dysbiosis and reduced butyrate levels. However, oral butyrate administration has limitations. This study explores a strategy for the targeted colonization of Clostridium butyricum (C. butyricum) spores in the colon, aiming to promote local butyrate production for AKI therapy and elucidate its renoprotective mechanism. Methods: Gut microbiota and butyrate levels were analyzed in AKI patients and mice. Multiple AKI models were used to evaluate the renoprotective effects of C. butyricum spores and butyrate. Kidney tubular epithelial cell (TEC)-specific GPR43 conditional knockout mice and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed to investigate the underlying molecular mechanisms. The inulin gel was used as a matrix to construct a spore delivery system (CBIN gels). Results: AKI is associated with reduced butyrate-producing bacteria and lower butyrate levels. C. butyricum spores overcame the limitations of oral butyrate, restoring butyrate levels and alleviating renal injury, inflammation, and lipid accumulation in AKI mice. Mechanistically, butyrate produced by C. butyricum spores activated GPR43 in TECs, which competitively bound to GRP75, disrupted aberrant ER-mitochondria contacts, reduced mitochondrial Ca2+ overload, and exerted renoprotection. CBIN gels promote the retention, proliferation, and germination of C. butyricum spores in the colon, thereby enhancing butyrate release and ultimately strengthening the renoprotective effects of the spores. Conclusions: Our findings suggest that the use of C. butyricum spores overcomes the limitations of oral butyrate. C. butyricum spores alleviate AKI by regulating ER-mitochondria contacts through the GPR43-GRP75 axis. The inulin gel-based CBIN gels enhance the renoprotective effects of C. butyricum spores, representing a promising therapeutic strategy.

ORGANISM(S): Mus Musculus

SUBMITTER: Xiaoming Meng  

PROVIDER: PXD077101 | iProX | Mon Apr 13 00:00:00 BST 2026

REPOSITORIES: iProX