Using a new RNA-based method, A*STAR researchers uncovered microbial activity on the skin that earlier methods could not capture, helping explain how microbes may protect or disrupt skin health.

Singapore – Scientists have long known that our skin is home to vast communities of bacteria, fungi and viruses. But knowing which microbes are present only tells part of the story. What matters just as much is which microbes are active, what genes they switch on, and how they interact with one another on the skin.

Researchers from the A*STAR Genome Institute of Singapore (A*STAR GIS) and the A*STAR Skin Research Labs (A*STAR SRL) have developed a new method to study RNA directly from microbes naturally found on the skin. Published in Nature Biotechnology, the study allows researchers to see not just which microbes are present, but which are active and what they are doing.

Until now, most skin microbiome studies have relied on DNA-based methods, which identify microbes present on the skin but cannot show whether they are active or influencing skin health. Analysing microbial RNA on the skin has been far more difficult because skin samples contain very little microbial material, making it harder to detect microbial RNA in the first place. They also contain many human skin cells, whose genetic material can drown out the microbial RNA researchers are trying to detect. RNA is also fragile and breaks down easily, making it harder to recover high-quality material and generate reliable results. By overcoming these challenges, the new method offers a clearer and more functional picture of how skin microbes may protect health or contribute to disease.

Key findings:

Some of the skin’s most active microbes are not the most abundant
The study found that Malassezia fungi and Staphylococcus bacteria were highly active in many healthy individuals, even though they were not always the most common microbes on the skin. This suggests that microbes that appear less prominent may still play an important role in skin health and disease.
Skin microbes adapt to where they live on the body
The researchers found that microbes switch on different genes depending on the skin site they occupy. For example, microbes on the scalp expressed different lipid-related genes from those on the cheek, showing how they respond to local conditions and helping explain why skin conditions can vary across the body.
Skin microbes produce antimicrobial compounds, including previously unknown ones

The study also identified antimicrobial genes expressed by skin microbes directly on human skin, including previously uncharacterised compounds that may help microbes compete with one another. This offers new insight into how healthy skin microbial communities are maintained and could inform future targeted approaches to support skin health.

The study analysed five skin sites in 27 healthy adults, combining metagenomics, a DNA-based method used to identify which microbes are present, with metatranscriptomics, an RNA-based method used to show which are active. This revealed that microbial activity does not always match microbial presence, highlighting the added value of RNA-based analysis.

Dr Chia Minghao, Senior Scientist at A*STAR GIS, said: “With this workflow, we can now see what skin microbes are actually doing on the skin. That gives us a much richer picture of how microbial communities function, adapt to different skin sites, and potentially influence health and disease.”

By combining this workflow with genomics, metabolic modelling and culture-based experiments, researchers will now have a practical foundation for studying microbial activity directly in human skin. It could help them better understand how healthy skin microbiomes function, identify pathways linked to skin disease, and uncover molecules with potential therapeutic value. The team believes it could also support future research into common skin conditions such as acne, eczema and psoriasis, where microbial activity may matter as much as, or more than, microbial presence.

Dr Niranjan Nagarajan, Associate Director, AI & Compute, at A*STAR GIS, said: “This approach gives researchers and clinicians a new way to profile microbial activity directly on the skin. By revealing biological pathways linked to microbial activity and skin health, it can help identify markers and mechanisms that may be relevant for prediction, diagnosis and treatment.”

Moving forward, the team will continue refining the workflow and applying it in clinical studies to better understand how microbes influence skin health and disease, supporting more precise and personalised approaches to skin health.

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About A*STAR Genome Institute of Singapore (A*STAR GIS)

The A*STAR Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, A*STAR GIS pursues the integration of technology, genetics, and biology towards academic, economic and societal impact, with a mission to harness genomic technologies for a better Singapore and world.

Key research areas at the GIS include RNA & DNA Technologies, Single Cell & Spatial Technologies), Precision Medicine, Population Genomics, and AI & Compute. The genomics infrastructure at the GIS is also utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit www.a-star.edu.sg/gis.

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About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

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