Astaxanthin could regulate the gut-kidney axis to mitigate kidney injury in high-fat diet/streptozotocin-induced diabetic mice

Abstract

Abstract: Accumulating evidences have shown the beneficial effects of astaxanthin (AST) supplementation on metabolic diseases prevention and treatment. The goal of present study was to reveal the favorable interactions among AST supplementation, gut microbiota, and kidneys in vivo, so as to attenuate kidney impairment in diabetic mice. Twenty C57BL/6J mice were assigned to a normal control group and a diabetic model group induced by a high-fat diet plus low-dose streptozotocin, and then the diabetic mice were fed with a high-fat diet without or with AST [0.01% (AST_a) or 0.02% (AST_b)] for 12 weeks. When compared to the diabetes kidney disease (DKD) group, AST supplementation delayed the renal pathological progression, reduced fasting blood glucose (AST_b: 1.53-fold, p<0.05), repressed levels of lipopolysaccharide (LPS; AST_a: 1.24-fold, p=0.008; AST_b: 1.43-fold, p<0.001) and TMAO (AST_a: 1.51-fold, p=0.001; AST_b: 1.40-fold, p=0.003), inhibited IL-6 (AST_a: 1.40-fold, p=0.004; AST_b: 1.57-fold, p=0.001) and reactive oxygen species (ROS; AST_a: 1.30-fold, p=0.004; AST_b: 1.53-fold, p<0.001), as well as regulated the Sirt1/PGC-1α/NFκB p65 signaling pathway. Moreover, the results of 16S rRNA gene-based Illumina deep sequencing in each group revealed that dietary AST supplementation also favorably modulated the gut microbiota compared with the DKD group, as evidenced by the inhibition of the harmful bacteria Clostridium_sensu_stricto_1, Romboutsia, and Coriobacteriaceae_UCG-002, and the enhancement of the probiotics such as Lachnospiraceae_NK4A136_group, Roseburia, and Ruminococcaceae. Taken together, dietary AST supplementation could protect kidneys against inflammation and oxidative stress by adjusting the gut-kidney axis in diabetic mice.