FC 083PROBIOTIC L.CASEI ZHANG SLOWS THE PROGRESSION OF ACUTE AND CHRONIC KIDNEY DISEASE
Abstract Background and Aims The relationship between gut microbial dysbiosis and acute or chronic kidney disease is currently acknowledged to be a health concern which is characterized by immune dysregulation and metabolic disorder. However, the therapeutic strategies remain to be developed. In the present study, we examined the protective effects and mechanisms of action of probiotic Lactobacillus casei Zhang (L. casei Zhang) on bilateral renal ischemia-reperfusion (I/R)-induced injury in mice. Method We orally gavaged male C57BL/6 mice with or without L. casei Zhang and probiotic Lactobacillus acidophilus (L. acidophilus) for 4 weeks (1 × 109 CFU per day) prior to being subjected to ischemia-reperfusion (I/R)-induced injury. Serum, colons and renal samples were collected after 5 days and 28 days. The composition and abundance of gut microbiota was investigated by using 16S rRNA. LC-MS metabolomic analysis technology and GC-MS analysis technology were used to investigate the metabolic alterations. To define the intra-renal cell subsets that are involved in L. casei Zhang-induced renoprotection, we performed single-cell RNA-sequencing (scRNA-seq) of kidney samples dissected from L. casei Zhang pretreated mice at day 5 after I/R along with samples from non-treated controls. Results Compared to L.acidophilus, L. casei Zhang demonstrated superior capacity in restoring intestinal flora homeostasis, protecting intestinal mucosal barrier function and improving the disrupted metabolomic profile. L. casei Zhang not only elevated the short chain fatty acids (SCFAs) in serum and kidney, but also significantly increased nicotinamide, by which L. casei Zhang inhibited renal inflammatory response and alleviated the damage of renal tubular epithelial cells (TECs) via interacting with SCFAs receptors on macrophages and TECs, and activating NAD+ metabolism in injured kidneys. Conclusion These results show that oral administration of L. casei Zhang, by altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney injury and slow the progression of renal decline.