To investigate the effect of Clostridium butyricum on renal tissue of db/db mice and to explore its mechanism.

Fourteen-week-old db/db mice were divided into db/db group(n=10) and db/db+ Cb group(n=7) according to random number table method. Age-matched db/m mice were selected as the normal control group. The db/m and db/db mice were administered 0.9% sodium chloride solution by gavage, while the db/db+ Cb mice were administered an equivalent amount of Clostridium butyricum solution by gavage for 8 weeks. Serum creatinine , fasting blood glucose, urinary albumin to creatinine ratio(ACR) and other biochemical indicators were also detected. HE staining was used to observe the pathological changes of kidney tissue. The expressions of peroxisome proliferators-activated receptor γ coactivator-1α(PGC-1α) mRNA were detected by realtime PCR, while the expressions of nuclear factor-κB(NF-κB), glucagon-like peptide 1 receptor(GLP-1R), and adenosine monophosphate-activated protein kinase(AMPK) in kidney tissue were determined by immunohistochemistry and Western blotting. The levels of intestinal flora, serum and fecal short-chain fatty acids(SCFAs) were measured by 16S rRNA, liquid chromatograph-mass spectrometer, and gas chromatograohy-mass spectrometry respectively.

Compared to db/db mice, db/db+ Cb mice showed improvement in general condition after supplementation with Clostridium butyricum. Fasting blood glucose, blood urea nitrogen, albumin-to-creatinine ratio(ACR), blood creatinine, and levels of interleukin-6(IL-6) in kidney tissue were reduced(all P<0.05). The pathology showed various degrees of amelioration of kidney tissue injury in mice. The expression of PGC-1α mRNA increased in kidney tissue(P<0.05). Decreased expression of NF-κB protein, as well as increased expression of GLP-1R and phosphorylated(p-)AMPK/AMPK protein(all P<0.05) were detected in kidney tissues. Clostridium butyricum modulated the composition of the gut microbiota with elevated total SCFAs in blood and feces.

Clostridium butyricum increased the expression of GLP-1R in kidney tissue, promoted AMPK phosphorylation, and alleviated renal tissue damage in mice. This suggests that it may be associated with regulating the abundance of SCFA-producing bacterial populations.

Diabetes Nephropathy; Clostridium butyricum; Intestinal flora; Short-chain fatty acids