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bioRxiv · 10.1101/2025.09.04.674196

Integrative Multi-omics Deciphers the Assembly Rules of the Human Skin Microbiome and Highlights Lipid-Mediated Niche Partitioning

Chen, H.·Luo, W.·Guo, Z.·Li, Z.·Feng, J.·Cao, S.·Wang, Q.·Gu, Z.·Krutmann, J.·Wang, J.·Han, L.·Guo, Y.·Xia, J.
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Abstract

Understanding the ecological assembly mechanisms of microbial communities is critical for deciphering host-microbiota interactions, however, such processes remain poorly characterized in cutaneous ecosystems. By profiling a non-industrialized rural cohort, this study deciphers the assembly rules governing the human skin microbiome and reveals an evolutionarily conserved core microbiota structured by niche selection. Microbial -diversity peaks when C. acnes and M. osloensis reach equilibrium, supporting the Intermediate Disturbance Hypothesis. Host lipids, rather than aqueous compounds, emerged as the primary drivers of microbial niche partitioning. We further demonstrate that C. acnes and Malassezia restricta function as core metabolic engineers, expressing diverse lipases that hydrolyze triglycerides (TGs) into free fatty acids (FFAs), thereby maintaining skin surface lipid homeostasis ([~]85% TG + FFA). Notably, virtually all skin surface FFAs are microbially derived and function as "public goods", enabling cross-feeding that supports auxotrophic members and fosters mutualistic interactions. Importantly, in vitro coculture experiments confirm that C. acnes establish a survival niche for M. restricta. Our findings support a paradigm shift from a taxonomic to a functional understanding of the skin ecosystem, underscoring microbial lipid metabolism as a central orchestrator of ecological stability and a promising target for therapeutic intervention. O_FIG O_LINKSMALLFIG WIDTH=182 HEIGHT=200 SRC="FIGDIR/small/674196v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@1274fa5org.highwire.dtl.DTLVardef@1ddfa07org.highwire.dtl.DTLVardef@49f917org.highwire.dtl.DTLVardef@807a14_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHIC ABSTRACTC_FLOATNO C_FIG

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Chen, H., Luo, W., Guo, Z., Li, Z., Feng, J., Cao, S., Wang, Q., Gu, Z., Krutmann, J., Wang, J., Han, L., Guo, Y., Xia, J.. 2025-09-07. Integrative Multi-omics Deciphers the Assembly Rules of the Human Skin Microbiome and Highlights Lipid-Mediated Niche Partitioning. https://doi.org/10.1101/2025.09.04.674196

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