Inulin gel-mediated delivery of Clostridium butyricum spores protects against acute kidney injury via regulation of ER-mitochondria contacts

ABSTRACT: Acute kidney injury (AKI) progression is closely associated with gut microbiota dysbiosis. However, the detailed mechanism remains unclear. In this study, we found that patients with AKI had decreased beneficial bacteria and reduced butyric acid levels in the intestine. Furthermore, butyrate alleviates renal injury and inflammation in AKI in mice. Nevertheless, the oral administration of butyric acid is limited by its pungent odor and low bioavailability. Here, we utilize the tolerance of Clostridium butyricum (C. butyricum) spores to cross the gastric acid barrier and colonize the colon for local butyric acid production. Our results showed that C. butyricum spores increased butyric acid levels in the intestinal contents, serum, and renal tissue. Mechanistically, gut-derived butyric acid enters the systemic circulation and activates GPR43 in renal tubular epithelial cells. Activated GPR43 competitively binds GRP75, thereby disrupting pathological endoplasmic reticulum (ER)-mitochondria contacts at mitochondria-associated ER membranes (MAMs), which alleviates mitochondrial Ca2+ overload, attenuating renal injury, inflammation, and lipid accumulation in AKI. We also developed a C. butyricum spore@Inulin gels (CBIN gels) delivery system using an inulin gel matrix to enhance colonic retention and germination of C. butyricum spores, promoting butyric acid production, and ultimately improving renoprotective effects in AKI mice. This study demonstrates that targeted C. butyricum spore delivery via inulin gel ameliorates AKI by modulating ER-mitochondria contacts through the GPR43-GRP75 axis. These findings provide valuable insights and a theoretical foundation for the treatment of AKI.

INSTRUMENT(S): Gas Chromatography MS - positive - high-polarity

PROVIDER: MTBLS15607 | MetaboLights | 2026-09-17

REPOSITORIES: MetaboLights