bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.07.30.605752

Ganoderma lucidum alleviates kidney aging by modulating gut microbiota

Liu, X.·Zhao, J.·Liu, J.·Huang, Y.·Deng, W.·Yan, L.·Cui, M.·Xiao, H.
View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Liu, X., Zhao, J., Liu, J., Huang, Y., Deng, W., Yan, L., Cui, M., Xiao, H.. 2024-07-31. Ganoderma lucidum alleviates kidney aging by modulating gut microbiota. https://doi.org/10.1101/2024.07.30.605752

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗
bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗