Research Projects

RATIONALE Chronic Kidney disease (CKD) irreversibly changes the function and structure of the kidneys and affects >10% of the population worldwide. It is a progressive disease and in most cases ultimately leads to renal fibrosis. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin–angiotensin–aldosterone system inhibitors, drugs to control blood pressure and proteinuria control. However, majority of the patients progress to end stage kidney disease due to the accumulation of uremic toxins and require intense treatments such as dialysis or kidney transplantation. The existing therapies are insufficient for the removal of the harmful protein-bound uremic toxins and there is an urgent need to search for new therapies or interventions to reduce the accumulation of the toxins and improve the treatment strategies in patients with CKD. NOVELTY The role of uremic toxins in CKD caused by gut dysbiosis and microbial derived metabolites, in the etiopathogenesis of CKD progression has been studied. However, to the best of our knowledge, intervention by therapeutic targets that could be effectual in the prevention of CKD progression, by investigating the gut microbiota and microbial derived metabolites in Indian CKD have not yet been explored. OBJECTIVES The discovery phase of the study will include identification of therapeutic targets by deciphering the renal function associated bacterial population in the feces of CKD patients and investigating the circulating differential renal function associated metabolites. In the validation phase, the Adenine-induced CKD rat model will be used to study the gut microbiota profile and differential renal function associated metabolites, followed by assessing the therapeutic effect of the identified bacteria in CKD rats. Further, the metabolic pathways will also be explored for future therapeutic development. METHODS Multi-omics approach by integrating 16S rRNA metagenomics to gain insights into the microbial communities and dominant taxa related to CKD progression which will be augmented with LC-MS based metabolomics for the functional potential of the microbes in CKD progression. EXPECTED OUTCOMES This study will provide the understanding on: • Role of specific microbiota and metabolites: Identifying which specific microbiota species and metabolites play a regulatory role in CKD progression • Influence of interventions: Exploring the effects of therapeutic intervention that regulate the gut microbiota, which may help in personalized therapeutic strategies. • Mechanisms of gut microbiota modulation: Investigating the influence of the gut microbiota and the metabolic pathways through which it regulates the host disease mechanisms.