Targeting the gut‒kidney axis for lupus nephritis treatment: multimechanism regulatory strategies and evidence from Traditional Chinese medicine

Lupus nephritis (LN) treatment remains challenging because of the limited efficacy and substantial side effects of conventional immunosuppressive therapies. Traditional Chinese medicine (TCM), with its holistic and multitarget approach, offers unique therapeutic potential. The emerging gut-kidney axis theory provides a new framework for understanding LN pathogenesis by linking gut dysbiosis and intestinal barrier injury to renal inflammation. This review systematically examines the role of gut-kidney axis dysregulation in LN progression and establishes connections between the TCM spleen-kidney correlation theory and this modern concept. Accumulating evidence suggests that TCM compounds and active ingredients alleviate renal injury and improve LN through multiple mechanisms. TCM compounds modulate the gut microbiota composition, enhance intestinal barrier integrity, reduce endotoxin translocation, and suppress systemic inflammation. These findings position the gut-kidney axis as a critical target for TCM intervention. Through multicomponent synergy, TCM restores gut homeostasis and inhibits aberrant immune responses. Future studies should integrate multiomics approaches, including metagenomics and metabolomics, and prospective clinical trials should dynamically track the gut microbiota and metabolite profiles in LN patients. Such investigations will clarify the precise mechanisms by which TCM modulates the gut-kidney axis and facilitate the development of personalized TCM-based therapeutic strategies.