The Gut–Kidney Dialogue: Unraveling the Microbial Symphony in Renal Fibrosis

ABSTRACT Renal fibrosis is a maladaptive pathological endpoint common to the diverse etiologies of chronic kidney disease (CKD), resulting in irreversible nephron loss and functional decline. Emerging evidence has highlighted the potential role of the gut microbiota in renal fibrosis through bidirectional interactions between the gut and kidney. In animal models, broad‐spectrum antibiotic regimens have been confirmed to attenuate renal fibrosis, whereas fecal microbiota transplantation from fibrotic donors transmits renal disease in recipient germ‐free mice, providing rudimentary evidence of microbial causality. Human‐based studies have demonstrated that, in patients with CKD exhibiting progressive fibrosis, there are modifications in the composition of the gut microbiota, including decreased microbial variety and shifts in the distribution of specific bacterial groups. Furthermore, metabolomic profiling revealed that the severity of fibrosis was independently predicted by increased levels of circulating trimethylamine N‐oxide and indoxyl sulfate. Preliminary clinical studies exploring the therapeutic potential of regulating the gut microbiota have demonstrated promising results. Interventions, such as high‐purity probiotic formulations, result in improved renal function and decreased levels of fibrotic markers. These findings suggest a potential correlation between gut microbiota dysbiosis and renal fibrosis. However, further research is necessary to determine the causal correlations, elucidate the underlying mechanisms, and identify specific microbial species and metabolites related to the regulation of renal fibrosis. This review provides a systematic summary of the current understanding of the important connection between gut microbiota dysbiosis and renal fibrosis. Understanding the influence of gut microbiota on renal fibrosis may open new avenues for the development of innovative therapeutic strategies to prevent or manage renal fibrosis and its associated complications.