Gut microbiome reveals the impact of Microcystin-LR on kidney disease progression though gut–kidney axis
Description
The gut-kidney axis plays a crucial role in kidney disease progression, driven by interactions between the gut microbiome and host proteome. This study explores the impact of microcystin-LR (MC-LR), a potent cyanotoxin, on kidney disease progression through its effects on the gut microbiome and host proteome. While the nephrotoxic effects of MC-LR are established, its role in disrupting the gut-kidney axis remains less understood. Twenty animals were divided into four groups: 1) control, 2) Adenine-treated (Adenine), 3) MC-LR-treated (Microcystin), and 4) a combination of adenine and MC-LR (Combination). DNA and protein were extracted from fecal samples, and 16S rRNA gene sequencing (V3-V4 region) along with LC/MS/MS analysis were performed. The results showed significant alterations in gut microbial communities, with a notable increase in Bacillaceae, Enterobacteriaceae, and Bacteroidaceae in the combination group. Metaproteomic analysis of the host gut proteome revealed disruptions in proteins linked to gut barrier integrity, inflammation, and immune responses, such as nuclear receptor-interacting factor 3 (Itgb3bp) and Thioredoxin-interacting protein (TXNIP). This suggests that MC-LR compromises the gut barrier, allowing microbial products to enter circulation, which accelerates kidney disease progression. Protein-chemical interaction networks further clarified the pathways linking inflammation, gut leakiness, and kidney damage. In conclusion, this study underscores the role of MC-LR in promoting kidney disease via the gut-kidney axis, identifying gut barrier integrity and inflammation as key therapeutic targets for kidney disease management.