Probiotics restore enteric HDL3 secretion and improve prognosis in patients with end-stage renal disease

Randomized double-blind trials have shown that probiotic mixtures significantly increase high-density lipoprotein (HDL) levels and reduce the risk of cardiovascular disease mortality in end-stage renal disease (ESRD) patients. Meta-analysis with prospective cohort studies further confirms that elevated HDL is a protective factor for ESRD outcomes. In severe renal injury models, including 5/6 nephrectomy and apolipoprotein E-deficient (ApoE^-/- ) mice, probiotics restored cardiac function, mirroring the cardioprotective effects seen in humans. Mechanistic studies indicate that probiotics enhance intestinal HDL3 production through the insulin-mediated SP1(P)-CYP27A-LXRα/β-ABCA1 pathway, thereby maintaining HDL metabolic homeostasis. This study reveals a novel link between probiotic intervention and host cholesterol metabolism, offering a previously unexplored strategy for reducing cardiovascular risk in ESRD patients.