title: The balance of metagenomic elements shapes the skin microbiome in acne and health.
abstract: Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Barnard
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
authors.forename: Baochen
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Kang
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Craft
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.|UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, California, USA.
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
mesh_terms: D000152:Acne Vulgaris / Q000382:microbiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001435:Bacteriophages / Q000302:isolation & purification*; D016022:Case-Control Studies; D015331:Cohort Studies; D064368:Healthy Volunteers; D006801:Humans; D054892:Metagenome; D056186:Metagenomics; D064307:Microbiota; D008875:Middle Aged; D011425:Propionibacterium acnes / Q000302:isolation & purification* / Q000821:virology; D017422:Sequence Analysis, DNA; D012867:Skin / Q000382:microbiology*; D014774:Virulence; D055815:Young Adult