Scientists at the A*STAR Genome Institute of Singapore and A*STAR Skin Research Labs have developed a novel workflow to analyze microbial RNA collected directly from human skin, offering unprecedented insights into active gene expression rather than just microbial presence. Published in Nature Biotechnology on August 28, 2025, the research utilized metatranscriptomics across five skin sites in 27 healthy adults to reveal a striking mismatch where population abundance did not correlate with actual biological activity.
The researchers discovered that while Cutibacterium acnes accounted for 46% to 90% of microbial DNA, it contributed only 2% to 31% of RNA activity, whereas Malassezia fungi and Staphylococcus bacteria generated unexpectedly large shares of transcripts. Furthermore, microbial gene expression varied sharply across body sites such as the scalp, cheek, forearm, inner elbow, and toe web, driven by local environmental factors like oils, moisture, and oxidative stress exposure.
The study successfully detected active genes producing antimicrobial substances, including previously uncharacterized bacteriocins deployed against microbial competitors, identifying over 20 genes that mediate skin organism interactions. These findings provide critical starting points for discovering natural antimicrobial molecules and developing precision treatments that influence targeted microbes without broadly disrupting the skin microbiome.
This pioneering approach bridges the gap between static microbiome cataloging and functional biological activity, holding immense potential for future clinical studies on inflammatory skin conditions like acne, eczema, and psoriasis. By revealing biological pathways and markers linked to microbial behavior and skin health, clinicians can eventually support more precise, personalized diagnostic and therapeutic strategies.