Cited by 18Dermatology and Skin DiseasesGenomics and Phylogenetic StudiesMicrobial Community Ecology and Physiology

Skin metatranscriptomics reveals a landscape of variation in microbial activity and gene expression across the human body

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Chia, Minghao, Ng, Amanda Hui Qi, Ravikrishnan, Aarthi, Mohamed Naim, Ahmad Nazri, Wearne, Stephen, Common, John, Nagarajan, Niranjan·2026·Nature Biotechnology

Published version of a preprint

Abstract

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. Skin metagenomic and metatranscriptomic analysis shows divergence between microbial abundance and activity.

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Authors
Chia, M., Ng, A. H. Q., Ravikrishnan, A., Mohamed Naim, A. N., Wearne, S., Common, J., & Nagarajan, N.
Affiliations
Agency for Science, Technology and Research (SG)
Corresponding author
  • Chia, Minghao
  • Nagarajan, Niranjan
Venue
Nature Biotechnology
Published
2025-08-28
Volume
44
Issue
7
Pages
1178-1189
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W4413772111
Cited by
18
References
118
Citations by year
2026: 13 · 2025: 5
FWCI
17.25
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
Funders
  • National Research Foundation (NRFI09-0015)
  • Agency for Science, Technology and Research (H22/J1/a0/040, H1701a0004)
  • National Science Council
  • National University Health System
  • Medical Research Council
  • National Medical Research Council (H22J1a0040)
  • Lee Kong Chian School of Medicine, Nanyang Technological University
  • Biomedical Research Council (H17/01/a0/004)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
Keywords
skin microbiome, microbial gene expression, Staphylococcus, Malassezia, antimicrobial genes, bacteriocins, microbial interactions, skin commensals
MeSH terms
Skin Microbiome, Humans, Skin, Staphylococcus, Gene Expression Profiling, Metagenome, Metagenomics, Transcriptome, Microbiota

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