Gut microbiota and their metabolites play a key role in kidney health, particularly through gut-kidney axis interactions. Despite studies revealing the potential renal benefits of beneficial bacteria, it has not been clarified whether beneficial bacteria pre-treatment can exert a protective effect against predictable ureteral obstruction disease by modulating gut microbiota.

The present study used a unilateral ureteral obstruction (UUO) rat model and pre-treatment with the short-chain fatty acids (SCFAs)-producing bacterium Clostridium butyricum. The protective effect on the kidney was assessed by renal function and renal histopathologic staining. Feces were collected for 16SrRNA sequencing, and serum was analyzed by gas chromatography-mass spectrometry (GC-MS) and biomarker detection. Renal tissue senescence and apoptosis indices were also detected, as well as the assessment of intestinal permeability, while the levels of renal tissue histone deacetylases (HDACs) were detected.

Clostridium butyricum pre-treatment reduced serum creatinine and urea nitrogen levels, attenuated inflammation and oxidative stress, mitigated renal injury and fibrosis, as well as attenuated renal senescence and apoptosis, and improved intestinal permeability in UUO rats. 16S rRNA sequencing showed an increase in SCFAs-producing beneficial bacteria after Clostridium butyricum pretreatment, and GC-MS showed a significant increase in butyric and caproic acid content. In addition, the detection of HDACs showed that Clostridium butyricum pretreatment resulted in decreased levels of HDAC4 and HDAC10 in the kidneys of UUO rats.

Our study confirms that in UUO rats, clostridium butyricum pre-treatment attenuates renal injury and aging by modulating the gut microbiota -SCFAs-HDACs axis.