On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis.

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.

The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment.

Background: Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics. Objectives: To characterize changes in the skin microbiome during treatment for AD. Methods: The skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification. Results: We included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment. Conclusions: There are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

Parasitic Protozoa and Interactions with the Host Intestinal Microbiota.

Parasitic protozoan infections represent a major health burden in the developing world and contribute significantly to morbidity and mortality. These infections are often associated with considerable variability in clinical presentation. An emerging body of work suggests that the intestinal microbiota may help to explain some of these differences in disease expression. The objective of this minireview is to synthesize recent progress in this rapidly advancing field. Studies of humans and animals and in vitro studies of the contribution of the intestinal microbiota to infectious disease are discussed. We hope to provide an understanding of the human-protozoal pathogen-microbiome interaction and to speculate on how that might be leveraged for treatment.