Ganoderma lucidum alleviates kidney aging by modulating gut microbiota

BackgroundGanoderma lucidum, a renowned traditional Chinese medicine known for its multiple health benefits, including anti-aging effect, has the ability to influence gut microbiota. However, its specific role in alleviating aging via gut microbiota has not been thoroughly investigated. Here, we explored the impact of G. lucidum sporoderm-broken spore powder (Gl-SBSP) on kidney aging using naturally aged and radiation-induced premature senescence mouse models. MethodsWe analyzed gut microbiota through high-throughput sequencing in naturally aged and radiation-induced premature senescence mice after oral administration of Gl-SBSP. Additionally, untargeted metabolomics of the gut microbiome in naturally aged mice was performed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analyses. Transcriptomics was employed to systematically measure gene expression levels throughout kidney tissues. ResultsGl-SBSP effectively mitigated aging-related phenotypic changes and significantly alleviated kidney aging, although outcomes were mixed in the irradiation mouse model. Importantly, Gl-SBSP modulated gut bacterial composition, particularly enriching Lachnospiraceae in naturally aged mice and in radiation-induced premature senescence mice with positive prognostic outcomes. Nicotinamide riboside (NR), derived from Lachnospiraceae bacteria, was identified as a potential metabolite that promoted recovery of senescent kidneys and improved renal function, validated through in vitro and in vivo experiments. Transcriptome analysis revealed that NR regulates kidney steroid metabolism in aging. ConclusionOur findings suggest that Gl-SBSPs anti-aging effect is mediated by NR derived from the Lachnospiraceae family, influencing kidney steroid metabolism via the gut-kidney axis. These results provide new insights into the mechanisms underlying the anti-aging properties of Gl-SBSP. AbstractGanoderma lucidum, also known as "Linzhi," is a well-established traditional Chinese medicine renowned for its multiple health benefits and its influence on gut microbiota. In this study, we investigated the anti-aging effect of G. lucidum sporoderm-broken spore powder (Gl-SBSP) through the gut-kidney axis using naturally aged and radiation-induced premature senescence mouse models. Administration of Gl-SBSP not only effectively mitigated aging-related phenotypic changes but also significantly alleviated kidney aging, although outcomes were mixed in the irradiation model. Importantly, Gl-SBSP modulated gut bacterial composition, particularly enriching Lachnospiraceae in naturally aged mice and in radiation-induced premature senescence mice with favorable and long-lasting outcomes. Nicotinamide riboside (NR), derived from Lachnospiraceae bacteria, was identified as a potential metabolite that facilitated the rejuvenation of senescent kidneys and improved renal function through both in vitro and in vivo experiments. Further investigation revealed that NR regulated steroid metabolic process in kidney. Our findings suggest that the anti-aging effect of Gl-SBSP is mediated by NR derived from the Lachnospiraceae bacteria, thereby influencing kidney steroid metabolism through the gut-kidney axis. This study provides novel insights into the anti-aging mechanisms of Ganoderma.