Commensal microbes on the skin surface influence the behavior of cells below the epidermis. We hypothesized that bacteria or their products exist below the surface epithelium and thus permit physical interaction between microbes and dermal cells. Here, to test this hypothesis, we employed multiple independent detection techniques for bacteria including qPCR, Gram-staining, immunofluorescence, and in situ hybridization. Bacteria were consistently detectable within the dermis and dermal adipose of normal human skin. Sequencing of DNA from dermis and dermal adipose tissue identified bacterial 16S rRNA reflective of a diverse and partially distinct microbial community in each skin compartment. These results show the microbiota extends within the dermis, therefore enabling physical contact between bacteria and various cells below the basement membrane. These observations show that normal commensal bacterial communities directly communicate with the host in a tissue previously thought to be sterile.

Genome sequencing of single cells has a variety of applications, including characterizing difficult-to-culture microorganisms and identifying somatic mutations in single cells from mammalian tissues. A major hurdle in this process is the bias in amplifying the genetic material from a single cell, a procedure known as polymerase cloning. Here we describe the microwell displacement amplification system (MIDAS), a massively parallel polymerase cloning method in which single cells are randomly distributed into hundreds to thousands of nanoliter wells and simultaneously amplified for shotgun sequencing. MIDAS reduces amplification bias because polymerase cloning occurs in physically separated nanoliter-scale reactors, facilitating the de novo assembly of near-complete microbial genomes from single E. coli cells. In addition, MIDAS allowed us to detect single-copy number changes in primary human adult neurons at 1–2 Mb resolution. MIDAS will further the characterization of genomic diversity in many heterogeneous cell populations.