Combined metagenomic- and culture-based approaches to investigate bacterial strain-level associations with medication-controlled mild-moderate atopic dermatitis
Bibliographic record
Abstract
ABSTRACT Background The skin microbiome is disrupted in atopic dermatitis (AD). Existing research focuses on moderate-severe, unmedicated disease. Objective Investigate metagenomic- and culture-based bacterial strain-level differences in mild, medicated AD, and the effects these have on human keratinocytes (HK). Methods Skin swabs from anterior forearms were collected from 20 pediatric participants; 11 participants with AD sampled at lesional and nonlesional sites and 9 age- and sex-matched controls). Participants had primarily mild-moderate AD and maintained medication use. Samples were processed for microbial metagenomic sequencing and bacterial isolation. Isolates identified as S. aureus were tested for enterotoxin production. HK cultures were treated with cell free conditioned media from representative Staphylococcus species to measure barrier effects. Results Metagenomic sequencing identified significant differences in microbiome composition between AD and control groups. Differences were seen at the species- and strain-levels for Staphylococci , with S. aureus only found in AD participants and differences in S. epidermidis strains between control and AD swabs. These strains showed differences in toxin gene presence, which was confirmed in vitro for S. aureus enterotoxins. The strain from the most severe AD participant produced enterotoxin B levels >100-fold higher than the other strains (p<0.001). Strains also displayed differential effects on HK metabolism and barrier function. Conclusions Strain level differences in toxin genes from Staphylococcus strains may explain varying effects on HK, with S. aureus and non-aureus strains negatively impacting viability and barrier function. These differences are likely important in AD pathogenesis. KEY MESSAGES Staphylococcal strain effects, more so than species effects, impact keratinocyte barrier function and metabolism, suggesting that strain level differences, and not species-level, may be critical in AD pathogenesis. The microbiome from mild, medicated atopic dermatitis patients harbor Staphylococcus strains with detrimental effects on skin barrier, and may not only be mediated by S. aureus . CAPSULE SUMMARY Patients with mild atopic dermatitis controlled by medication may still harbor strains of Staphylococcus spp. that carry toxins that negatively impact skin barrier function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".