RESUMO
Metabolites from the gut microbiota define molecules in the gut-kidney cross talks. However, the mechanistic pathway by which the kidneys actively sense gut metabolites and their impact on diabetic chronic kidney disease (DCKD) remains unclear. This study is an attempt to investigate the gut microbiome metabolites, their host targeting genes, and their mechanistic action against DCKD. Gut microbiome, metabolites, and host targets were extracted from the gutMgene database and metabolites from the PubChem database. DCKD targets were identified from DisGeNET, GeneCard, NCBI, and OMIM databases. Computational examination such as protein-protein interaction networks, enrichment pathway, identification of metabolites for potential targets using molecular docking, hubgene-microbes-metabolite-samplesource-substrate (HMMSS) network architecture were executed using Network analyst, ShinyGo, GeneMania, Cytoscape, Autodock tools. There were 574 microbial metabolites, 2861 DCKD targets, and 222 microbes targeting host genes. After screening, we obtained 27 final targets, which are used for computational examination. From enrichment analysis, we found NF-ΚB1, AKT1, EGFR, JUN, and RELA as the main regulators in the DCKD development through mitogen activated protein kinase (MAPK) pathway signalling. The (HMMSS) network analysis found F.prausnitzi, B.adolescentis, and B.distasonis probiotic bacteria that are found in the intestinal epithelium, colonic region, metabolize the substrates like tryptophan, other unknown substrates might have direct interaction with the NF-kB1 and epidermal growth factor receptor (EGFR) targets. On docking of these target proteins with 3- Indole propionic acid (IPA) showed high binding energy affinity of -5.9 kcal/mol and -7.4kcal/mol. From this study we identified, the 3 IPA produced by F. prausnitzi A2-165 was found to have renal sensing properties inhibiting MAPK/NF-KB1 inflammatory pathway and would be useful in treating CKD in diabetics.
RESUMO
BACKGROUND AND AIM: The symptoms of acute kidney injury (AKI) include a sudden drop-in glomerular filtration rate (GFR), a rise in serum creatinine (sCr), blood urea nitrogen (BUN), and electrolytes, which leads to a rapid loss of kidney function. Chronic kidney disease progresses when AKI symptoms persist for over three months or 90 days. Numerous prevalent secondary risk factors, including diabetes, hypertension, obesity, and heart illness, are directly or indirectly linked to the development of AKI and the switch from AKI to CKD. Recently, the change of intestinal bacteria known as "gut dysbiosis" has been linked to distant organ dysfunction, including the heart, lungs, kidneys, and brain. Indirectly or directly, gut dysbiosis contributes to the progression of CKD and AKI. However, the effects of gut dysbiosis and the mechanism of action in the progression from AKI to CKD are unknown or need further investigation. The mechanism by which gut dysbiosis initiates AKI's progression to CKD should be explicitly concerned. The review primarily focuses on the action of gut dysbiosis in kidney disease, the effects of dysbiosis, the characterisation of dysbiosis and its pathogenic products, the various pathogenic routes and mechanism involved in expediting the transition from AKI to CKD. CONCLUSION: We identified and briefly reviewed the impacts of dysbiosis in various situations such as hypoxia, mitochondrial induced reactive oxygen species (mtROS), aryl hydrocarbon receptor (AhR) activation and microbiota derived uremic toxemic substances profoundly to push AKI to CKD conditions.