Chia Minghao, Ng Amanda Hui Qi, Ravikrishnan Aarthi, Mohamed Naim Ahmad Nazri, Wearne Stephen, Common John, Nagarajan Niranjan
Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
Nat Biotechnol. 2025 Aug 28. doi: 10.1038/s41587-025-02797-4.
Metatranscriptomics methods for the skin are hampered by low microbial biomass, contamination with host cells and low RNA stability. In this study, we developed a robust, clinically tractable skin metatranscriptomics workflow that provides high technical reproducibility of profiles, uniform coverage across gene bodies and strong enrichment of microbial mRNAs. Paired application of this protocol with metagenomics to five skin sites in a cohort of 27 healthy adults identifies a notable divergence between transcriptomic and genomic abundances. Specifically, Staphylococcus species and the fungi Malassezia had an outsized contribution to metatranscriptomes at most sites, despite their modest representation in metagenomes. Species-level analysis shows signatures of microbial adaptation to their niches. Gene-level analysis identifies diverse antimicrobial genes transcribed by skin commensals in situ, including several uncharacterized bacteriocins. Correlation of microbial gene expression with organismal abundances uncovers more than 20 genes that putatively mediate interactions between microbes. This work highlights how skin metatranscriptomics identifies active species and microbial functions in situ.
皮肤宏转录组学方法受到微生物生物量低、宿主细胞污染和RNA稳定性低的阻碍。在本研究中，我们开发了一种强大的、临床适用的皮肤宏转录组学工作流程，该流程可提供高度的技术重现性、基因体的均匀覆盖以及微生物mRNA的强烈富集。将该方案与宏基因组学配对应用于27名健康成年人队列中的五个皮肤部位，发现转录组丰度和基因组丰度之间存在显著差异。具体而言，葡萄球菌属和马拉色菌属真菌在大多数部位的宏转录组中贡献巨大，尽管它们在宏基因组中的占比不大。物种水平分析显示了微生物对其生态位的适应特征。基因水平分析确定了皮肤共生菌原位转录的多种抗菌基因，包括几种未表征的细菌素。微生物基因表达与生物体丰度的相关性揭示了20多个可能介导微生物间相互作用的基因。这项工作突出了皮肤宏转录组学如何原位识别活跃物种和微生物功能。
