Ganoderma lucidum sporoderm-broken spore powder alleviates kidney aging by modulating gut microbiota.

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Citation abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum), a revered medicinal mushroom in traditional Chinese medicine (TCM), has been historically documented for its anti-aging properties and nephroprotective effects. Nevertheless, its mechanism of action through gut microbiota modulation to attenuate renal and systemic aging remains incompletely understood.

AIM OF THE STUDY: To elucidate the gut microbiota-dependent anti-aging mechanisms of G. lucidum on renal and systemic senescence using integrative multi-omics approaches.

MATERIALS AND METHODS: We systematically evaluated the anti-aging efficacy of G. lucidum sporoderm-broken spore powder (Gl-SBSP) via the gut-kidney axis in naturally aged and radiation-induced premature senescence mouse models. Renal aging phenotypes were assessed using histopathological analyses (hematoxylin-eosin and Masson staining), immunofluorescence (IF), complete blood counts, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (RT-qPCR). Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified microbiota-derived metabolites, functionally validated in HK-2 cells and aged mice. Mechanistic pathways were elucidated via transcriptomic analysis.

RESULTS: Gl-SBSP attenuated kidney aging phenotypes in both natural aging and irradiation models. It selectively enriched Lachnospiraceae, whose metabolite nicotinamide riboside (NR) elevated renal NAD + levels (in vitro and in vivo), rejuvenated senescent kidneys, and improved renal function through steroid metabolism regulation.

CONCLUSION: Gl-SBSP counters renal aging through Lachnospiraceae-driven gut microbiota remodeling, where NR serves as the core rejuvenating metabolite. By activating NAD + biosynthesis and modulating steroid metabolism via the gut-kidney axis, this mechanism offers a novel therapeutic strategy against age-related renal decline and validates Ganoderma lucidum's ethnopharmacological relevance.