Ganoderma lucidumalleviates kidney aging by modulating gut microbiota

Abstract

AbstractBackgroundGanoderma 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 ofG. lucidumsporoderm-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 ofGl-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 throughin vitroandin vivoexperiments. Transcriptome analysis revealed that NR regulates kidney steroid metabolism in aging.ConclusionOur findings suggest thatGl-SBSP’s 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 ofGl-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 ofG. lucidumsporoderm-broken spore powder (Gl-SBSP) through the gut-kidney axis using naturally aged and radiation-induced premature senescence mouse models. Administration ofGl-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 bothin vitroandin vivoexperiments. Further investigation revealed that NR regulated steroid metabolic process in kidney. Our findings suggest that the anti-aging effect ofGl-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 ofGanoderma.