Topical tretinoin alters skin microbiota in patients with mild acne

than the median in healthy controls (ie, untreated), demonstrating that there is a higher skin burden of Kingella on patients with acne at baseline. On visit 2, there was no statistically significant difference between the relative abundances of Kingella between patients with acne who were treated with topical tretinoin, Altreno, for approximately 90 days and healthy controls without any therapeutic intervention. On visit 3, after patients with acne discontinued the tretinoin therapy for approximately 60 days, the relative abundance of Kingella of patients with acne was unchanged from that of patients with acne on visit 2. CLR , Centered log-ratio; padj , adjusted P -value.


Topical tretinoin alters skin microbiota in patients with mild acne
To the Editor: There is increasing evidence of the role that the skin microbiota plays in the pathogenesis of acne vulgaris. 1We hypothesize that topical tretinoin without known antibacterial properties can induce alteration of the skin microbiome in patients with acne.We conducted a study to assess the changes in the skin microbiota associated with therapeutic response in patients with acne, who were treated with tretinoin 0.05% lotion, Altreno (Ortho Dermatologics).
We prospectively recruited subjects who met our inclusion/exclusion criteria.For visit 1, we swabbed 1 cheek of all subjects to assess their baseline skin microbiomes.For acne patients, we repeated the skin microbiome collection after they underwent treatment with tretinoin for ;90 days (visit 2) and after they discontinued tretinoin for ;60 days (visit 3).We also graded their acne severity using the Physician Global Assessment scoring system. 2 For control subjects, we repeated the skin microbiome collection after ;90 days (visit 2) without any therapeutic intervention to serve as an internal control; therefore, additional time point (visit 3) was not necessary.The skin swab samples were sent to Diversigen, Inc for downstream processing and analysis (Supplementary Materials, available via Mendeley at https://doi.org/10.17632/kv56sxty73.1).
We recruited 12 control subjects and 12 acne patients; 4 control subjects and 4 acne patients were lost to follow-up after visit 1 (Table I).At baseline, relative abundance of Kingella at the genus level was 5.8-fold higher in acne patients compared to that in healthy controls (visit 1) (Fig 1).Then, after treatment with tretinoin, there was no statistically significant difference in the relative abundance of Kingella between acne patients and healthy controls (visit 2) (Fig 1).Finally, after discontinuation with tretinoin, there was no statistically significant difference in the relative abundance of Kingella in patients with acne between visit 2 and visit 3 (Fig 1).The P value was set at \.15.X.We found 3additional taxa at the family level to be significant (Supplementary Results, available via Mendeley at https://doi.org/10.17632/kv56sxty73.1).
Our study was limited by a small sample size and a high dropout rate, and may have failed to find any small, yet significant, differences in the alpha and beta diversity measures (Supplementary Materials, available via Mendeley at https://doi.org/10.17632/kv56sxty73.1).Additionally, our acne cohort was homogenous, mainly of young female subjects with mild acne amenable to topical therapy only.Therefore, our study findings may not translate to a broader population.Despite these limitations, we observed that the acne patients at baseline had a higher skin burden of Kingella compared to the control subjects.With tretinoin treatment in patients with acne, the relative abundance of Kingella on the skin normalized to the level similar to the control subjects without acne.Moreover, the therapeutic effect of tretinoin on the skin microbiota (ie, Kingella) was maintained for 60 days despite discontinuation of its use.Several well-known species of Kingella are pathogenic; however, recent studies Relative abundance of Kingella in untreated vs Altreno.The relative abundance was represented on the Y-axis as a centered log-ratio transformation of the read count of Kingella over the read counts of all other taxa within each sample.On visit 1, the median of centered log-ratioetransformed abundances of Kingella in patients with acne (ie, Altreno) was 5.8-fold higher than the median in healthy controls (ie, untreated), demonstrating that there is a higher skin burden of Kingella on patients with acne at baseline.On visit 2, there was no statistically significant difference between the relative abundances of Kingella between patients with acne who were treated with topical tretinoin, Altreno, for approximately 90 days and healthy controls without any therapeutic intervention.On visit 3, after patients with acne discontinued the tretinoin therapy for approximately 60 days, the relative abundance of Kingella of patients with acne was unchanged from that of patients with acne on visit 2. CLR, Centered log-ratio; padj, adjusted P-value.
have shown that Kingella at the genus level is found in the healthy skin microbiome. 3,4Overall, our findings demonstrate that topical application of tretinoin may alter the skin microbiome in patients with acne, suggesting a potential additional therapeutic mechanism of tretinoin.

Fig 1 .
Fig 1.Relative abundance of Kingella in untreated vs Altreno.The relative abundance was represented on the Y-axis as a centered log-ratio transformation of the read count of Kingella over the read counts of all other taxa within each sample.On visit 1, the median of centered log-ratioetransformed abundances of Kingella in patients with acne (ie, Altreno) was 5.8-fold higher than the median in healthy controls (ie, untreated), demonstrating that there is a higher skin burden of Kingella on patients with acne at baseline.On visit 2, there was no statistically significant difference between the relative abundances of Kingella between patients with acne who were treated with topical tretinoin, Altreno, for approximately 90 days and healthy controls without any therapeutic intervention.On visit 3, after patients with acne discontinued the tretinoin therapy for approximately 60 days, the relative abundance of Kingella of patients with acne was unchanged from that of patients with acne on visit 2. CLR, Centered log-ratio; padj, adjusted P-value.

Table I .
Acne status, demographic factors, and Physician Global Assessment scores of study subjects Martinez, MD, a Omkar Mayur, BS, a Kyla Pagani, BS, b Danitza Lukac, MD, c and Jean S. All patients gave consent for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available.IRB approval status: The study was approved by the Beth Israel Deaconess Medical Center Institutional Review Board (Protocol #: 2020P000595).