Association of Multi-Kingdom Skin Microbiota With Radiation Dermatitis in Patients With Breast Cancer After Reconstructive Surgery: A Prospective, Longitudinal Study

The clinical significance of multi-kingdom skin microbiota in acute radiation dermatitis (ARD) is not well understood. We hypothesized that skin microbiota is associated with ARD in patients with breast cancer (BC) undergoing radiation therapy (RT) after reconstructive surgery. A total of 412 skin microbiota samples from 103 patients, taken before and after RT, from both the treated and contralateral healthy sides, were analyzed using bacterial 16S ribosomal RNA (rRNA) V3-V4 region and fungal rRNA internal transcribed spacer (ITS) sequencing. ARD was graded using the Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG). Patients were divided into 2 groups: no or mild ARD subgroup (N_MD, RTOG grade 0-1) and significant ARD subgroup (SD, RTOG grade ≥ 2). Significant differences in skin microbiota were observed between the N_MD and SD subgroups, with Staphylococcus, Cutibacterium, and Malassezia genera enriched in SD and Ralstonia and Methyloversatilis enriched in N_MD. Network analysis revealed that interkingdom and intrakingdom ecological interactions were more notable and stable in N_MD than SD over the course of RT. Importantly, 2 dermotypes with robust patterns of microbial networks were identified, with the "D-dermotype" (highly diversified and dominated by Devosiaceae) composing entirely of N_MD. Dermatitis-prediction classifiers were constructed. Classifiers I and III, which included bacterial variables with or without fungal variables, performed significantly better than classifier II, which relied solely on fungal variables. Bacteria-based classifier I yielded the best area under the curve in the test set of 94.64% (95% confidence interval, 83.58%-100%). This prospective longitudinal study indicated an association between multi-kingdom skin microbiota and the development of significant ARD in patients with BC undergoing RT after reconstructive surgery, implying the possible application of skin microbiota in the prediction of ARD and microbial therapy in the management of ARD.