Metagenomic study of the human skin microbiome associated with acne

Abstract

The human microbiota contributes to our normal postnatal development and plays a significant role in defining our physiology. To understand the role of microbiota in human health and disease, we study the skin microbiome in pilosebaceous units (hair follicles) and its association with acne.Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting Propionibacterium acnes has been a mainstay treatment for more than 30 years.Our preliminary study shows that the microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome, with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome at the subspecies level by sequencing. Our preliminary study suggests that the microbiome associated with acne offers promise for understanding the correlation between the composition of the microbiome and human health and disease.The goal of the project is to determine whether the microbiota in the pilosebaceous units contributes to acne. We plan to investigate the microbiome associated with acne in three directions. First, we plan to investigate the strain diversity of P. acnes in a disease cohort and a normal cohort and examine whether certain strains of P. acnes are correlated with the disease. Second, we plan to investigate the non- P. acnes microbes in microcomedones and disease lesions and examine whether they correlate with acne pathogenesis. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host.During the first year of this project, two main questions were asked. 1. Are certain strains of P. acnes associated with acne, but rarely found in normal individuals? 2. If specific strains are associated with acne, what are the differences in their genetic composition compared to other P. acnes strains that are not associated with acne? We collected microcomedone samples from more than 100 subjects, including acne patients and normal individuals. Genomic DNA was extracted from each sample, and 16S rDNA was amplified using universal primers (8F and 1510R), cloned and sequenced using Sanger method. Approximately 384 near full length 16S rDNA sequences were obtained for each sample. Some of the microcomedone samples were also cultured under anaerobic condition to isolate different P. acnes strains. Sixty-eight isolates were selected for whole genome shotgun sequencing using Solexa/Illumina platform. By the end of the first year of the project, we completed the sequencing of more than 40,000 16S rDNA clones and 68 genomes of P. acnes isolates.