Abstract / Summary
IgA nephropathy (IgAN), the most common primary glomerular disease, involves mucosa-kidney axis dysregulation, with gut dysbiosis increasingly implicated in its pathogenesis. Certain Escherichia coli (E. coli) strains harbour virulence-associated features that promote intestinal colonization, barrier disruption and immune activation. Recent microbiome and metagenomic studies have reported an enrichment of E. coli in patients with IgAN, suggesting a potential link to the mucosa-kidney axis. Nevertheless, E. coli may contribute to IgAN through two major pathways. First, sustained LPS exposure may induce aberrant production of galactose-deficient IgA1 (Gd-IgA1) by stimulating B cells and activate the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages, thereby amplifying systemic and renal inflammation. Second, metabolic reprogramming is associated with increased circulating sphingosine-1-phosphate (S1P) and altered production of indole and trimethylamine (TMA); S1P may promote mesangial proliferation and fibrosis, whereas indole- and TMA-related pathways may contribute to tubulointerstitial injury and chronic kidney disease (CKD) progression. Beyond conventional gut microbiota-targeted interventions, emerging precision therapeutic strategies offer promising new directions for the etiological treatment of IgAN. This review summarizes E. coli virulence factors, pathogenesis, and host, environmental, and ecological factors driving its gut expansion in IgAN patients and outlines corresponding therapeutic strategies.