Date Published: February 28, 2018
Publisher: Public Library of Science
Author(s): Martin Glatz, Jay-Hyun Jo, Elizabeth A. Kennedy, Eric C. Polley, Julia A. Segre, Eric L. Simpson, Heidi H. Kong, Gilberto E Flores.
Emollients are a mainstay of treatment in atopic dermatitis (AD), a disease distinguished by skin bacterial dysbiosis. However, changes in skin microbiota when emollients are used as a potential AD preventative measure in infants remain incompletely characterized.
We compared skin barrier parameters, AD development, and bacterial 16S ribosomal RNA gene sequences of cheek, dorsal and volar forearm samples from 6-month-old infants with a family history of atopy randomized to receive emollients (n = 11) or no emollients (controls, n = 12). The emollient group had a lower skin pH than the control group. The number of bacterial taxa in the emollient group was higher than in the control group at all sites. The Streptococcus salivarius proportion was higher in the emollient versus control groups at all sites. S. salivarius proportion appeared higher in infants without AD compared to infants with AD. A decrease in S. salivarius abundance was further identified in a separate larger population of older children demonstrating an inverse correlation between AD severity at sampling sites and S. salivarius proportions.
The decreased skin pH and the increased proportion of S. salivarius after long-term emollient use in infants at risk for developing AD may contribute to the preventative effects of emollients in high-risk infants.
Atopic dermatitis (AD) is a chronic relapsing inflammatory pruritic skin disorder, which develops in the first six months of life in 45% of patients [1, 2]. Infants with a positive family history of atopy, i.e. first-degree relatives with AD, asthma, or allergic rhinitis, have an increased risk of developing AD with an odds ratio of 2–2.7 as compared to infants without a family history of atopy [3–5].
We analyzed skin swabs from infants aged 6 months who had been randomized shortly after birth to use (n = 11) or not use (n = 12) once daily application of an emollient to the whole-body surface. Skin samples were obtained from six sites: both left and right cheeks, dorsal forearms, and volar forearms. All 23 infants had a family history of atopy. Clinical evaluation showed one infant from emollient group and three from control group developed AD over the course of the study period. To exclude the potential confounding effects of AD on skin bacterial communities [15, 16], we limited the bacterial diversity analyses to infants who did not develop AD (emollient group n = 10, control group n = 9), unless otherwise specified. We sequenced 114 samples (19 subjects, left and right of three skin sites for a total of six skin sites) with a total of 643,999 high-quality reads of the V1-3 region of the bacterial 16S rRNA gene (5,529 median reads/sample, > 3,000 reads/sample in 95.6% of samples, 275bp median read length). The numbers of reads/sample were evenly distributed between the emollient and control groups (S1 Fig). Sequencing provided sufficient coverage to analyze dominant members of skin bacterial communities in the emollient group and controls at all three sampling sites (S2 Fig). Of the subjects, ten infants were female (43.5%) and no twins were in this cohort. At the sampling timepoint, breastfeeding was reported in twenty infants (87%), of which nine were exclusively breastfed. Stratified analyses based on diet was not feasible due to the mixed diets of breastfeeding, formula, and solid foods in this cohort.
AD is recognized as a complex multifactorial disease, including defective skin barrier and bacterial skin dysbiosis. Since emollients are considered an important therapeutic method to repair the impaired skin barrier in AD and are actively investigated as a method to prevent the development of AD , we sought to examine the effects of skin emollient use on the skin barrier and the skin bacterial communities by analyzing bacterial 16S rRNA gene sequences from skin swabs obtained from infants at-risk for developing AD.
The decreased skin pH and the increased bacterial richness and diversity associated with emollient use resembled the restoration of skin bacterial communities after skin-directed treatment of AD flares. S. salivarius had a statistically significantly higher relative abundance in the emollient versus the control group. S. salivarius proportion decreased with the development of AD in infants and of AD flares in children, whereas S. aureus showed the inverse development in children. The lower skin pH and immunomodulatory effects of S. salivarius may contribute to the therapeutic effects of emollient use in AD patients. Additional studies are needed to confirm pilot study results of emollients as a possible preventative therapy for AD and to investigate the mechanisms of how emollients affect the skin barrier and skin microbiota in an at-risk population.