The Interplay Among Gut Microbial Composition, Short-Chain Fatty Acid Metabolism and Gut-Kidney Oxidative Stress:...

Gut microbiota dysbiosis in the colon, leading to gut-kidney inflammatory responses, is a key cause of exacerbated diarrhea. The upstream mechanistic relationship between colonic microecological disturbance and gut-kidney interaction injury remains unclear.

In this study, a total of 20 KM mice were used. We established a mouse diarrhea model, analyzed colonic microbiota composition via 16S rRNA sequencing, quantified short-chain fatty acids (SCFAs) using gas chromatography-mass spectrometry (GC-MS), and measured sirtuin 3 (SIRT3), superoxide dismutase 2 (SOD2) protein levels, total SOD activity, and ROS levels in colonic and kidney tissues. Mouse physiological signs and histopathological changes were also evaluated.

In model mice, the relative expression levels of SIRT3 and SOD2 proteins in colon and kidney tissues were significantly decreased (P < 0.01). Similarly, the SOD enzyme activity also showed a significant reduction, with P < 0.05 in the colon and P < 0.01 in the kidney. In contrast, the intensity of ROS was significantly increased (P < 0.01). Colonic microbial diversity declined. Streptococcus showed a significant enrichment in the colon (P < 0.01), and the contents of propionic acid and isobutyric acid were significantly decreased (P < 0.05). A negative correlation was observed between the abundance of Streptococcus and SCFAs, and there were correlations between the abundance of Streptococcus and SOD enzyme activity in tissues as well as ROS intensity.

Therefore, we infer that there are associations between gut microbiota dysbiosis in the colon, altered levels of SCFAs, exacerbated gut-kidney oxidative stress responses, and the onset and progression of diarrhea.