title: Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.
abstract: Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aimed to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. Metatranscriptomic analysis revealed that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B12 biosynthesis pathway in the skin bacterium Propionibacterium acnes was significantly down-regulated in acne patients. We hypothesized that host vitamin B12 modulates the activities of the skin microbiota and contributes to acne pathogenesis. To test this hypothesis, we analyzed the skin microbiota in healthy subjects supplemented with vitamin B12. We found that the supplementation repressed the expression of vitamin B12 biosynthesis genes in P. acnes and altered the transcriptome of the skin microbiota. One of the 10 subjects studied developed acne 1 week after vitamin B12 supplementation. To further understand the molecular mechanism, we revealed that vitamin B12 supplementation in P. acnes cultures promoted the production of porphyrins, which have been shown to induce inflammation in acne. Our findings suggest a new bacterial pathogenesis pathway in acne and provide one molecular explanation for the long-standing clinical observation that vitamin B12 supplementation leads to acne development in a subset of individuals. Our study discovered that vitamin B12, an essential nutrient in humans, modulates the transcriptional activities of skin bacteria, and provided evidence that metabolite-mediated interactions between the host and the skin microbiota play essential roles in disease development.
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
authors.forename: Baochen
authors.initials: B
authors.lastname: Shi
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Erfe
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, 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, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA. UCLA-Department of Energy (DOE) Institute for Genomics and Proteomics, Los Angeles, CA 90095, USA. huiying@mednet.ucla.edu.
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
mesh_terms: D000152:Acne Vulgaris / Q000382:microbiology* / Q000473:pathology*; D000328:Adult; D016022:Case-Control Studies; D019587:Dietary Supplements; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D064307:Microbiota / Q000187:drug effects / Q000235:genetics*; D008954:Models, Biological; D009876:Operon / Q000235:genetics; D011166:Porphyrins / Q000096:biosynthesis; D011425:Propionibacterium acnes / Q000187:drug effects / Q000235:genetics; D012867:Skin / Q000382:microbiology*; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*; D014805:Vitamin B 12 / Q000096:biosynthesis / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D011166:Porphyrins; D014805:Vitamin B 12