Urinary Microbiome and Genetic Determinants in an Obstetric Disease, Kidney Stone Disease : A Review Article

Background: Kidney stone disease (KSD) is a significant health burden globally and its prevalence rate has been rising in developed and developing nations. Conventionally viewed as a mere physicochemical process, current developments have shown that it has a more complicated etiology due to the involvement of host genetics, metabolic factors, and the urinary microbiome. The fact that the urinary tract is not sterile has redefined the knowledge in stone pathogenesis, which is the interaction of microbial community and genetic determinant affecting crystal formation, urinary pH and oxalate metabolism.

Objective: The purpose of this review is to conduct a synthesis of existing evidence that connections urinary microbiota composition and host genetic architecture with the development, recurrence and phenotypic differences of kidney stones. It also addresses the concept of incorporating genome and microbial information in order to improve diagnosis, risk assessment and individualized preventive measures.

Recent Findings: Certain bacterial taxa, such as Enterococcus, Escherichia and Corynebacterium, to be linked with calcium oxalate and strauvite stones, whilst the loss of Lactobacillus and Prevotella species is linked with lower urinary citrate and higher indices of supersaturation. At the same time, genome-wide association studies (GWAS) have identified over 50 loci that are associated with susceptibility to stones, including the genes, which regulate calcium reabsorption (CLDN14, CASR), oxalate metabolism (AGXT, GRHPR) and uric acid processing (SLC2A9, SLC22A12). The genetic variants tend to interplay with the microbiome-dependent metabolic pathways and this gives an effect on the urinary composition and inflammation. Multi-omics systems that are integrative are now starting to uncover the role of gene-microbiome crosstalk in lithogenic environments and recurrence dynamics.

Conclusion: Knowledge of the urinary microbiome-genetic axis offers a novel paradigm to kidney stones research. Recent data indicate that, there is collaborative contribution of both host and microbial genomes in lithogenesis via metabolic, inflammatory, and immunomodulatory respondences. The combination of metagenomics, transcriptomics, and polygenic risk modelling in future translational studies can potentially set the basis of kidney stone disease prevention and management based on microbiome guidance and genotype specificity.