Bacteriotherapy with Staphylococcus hominis A9 (ShA9) is safe and shows potential clinical benefit for patients with atopic dermatitis (AD), investigators reported in Nature Medicine.
The randomized, double-blind phase 1 clinical trial assessed the safety and mechanisms of action of ShA9, a bacterium isolated from healthy human skin, as a topical therapy for AD. A total of 54 adult patients with moderate to severe AD of the ventral arms and who were culture positive for Staphylococcus aureus were enrolled in the study.
The participants were randomly assigned to the groups 2:1, with 36 receiving ShA9 (mean age, 29.4 years; 53% men; 42% White, 33% Asian) and 18 receiving vehicle alone (mean age, 26.6 years; 67% women; 44% White, 39% Asian).
Either ShA9 or vehicle was applied topically to the patients’ ventral forearms twice daily for 7 days. Blinded physician assessments and skin swabs were obtained at 24, 48, and 96 hours after the final dose on day 7, and telephone follow-up was conducted about 30 days after the last dose. The study’s primary endpoint was safety through day 8 compared with vehicle used alone.
The per-participant treatment-emergent adverse event (AE) rate was 0.19 for the ShA9 treatment group and 0.34 for the vehicle-only group (mean ratio, P =.075). No serious AEs were reported, and no AE led to discontinuation of treatment.
The patients were also required to fill out a daily diary, rating their eczema, swelling, and pain on a scale of 1 to 10, which captured the normal fluctuations of eczema and recorded these variations from baseline as AEs. According to these results, 83.3% of the participants receiving the vehicle only reported an AE, and 55.6% who received ShA9 reported an AE. Significantly fewer AEs were reported in those participants treated with ShA9 compared with participants treated with only vehicle (P =.044).
Treatment with ShA9 also reduced the colony-forming units of S aureus detectable on lesional and nonlesional skin on days 4 and 7 and after treatment in the 96-hour follow-up. In the 1-week application period, no significant improvement in clinical assessments was observed in the treatment cohort. However, a post-hoc analysis of a subgroup of AD participants whose skin was colonized by S aureus sensitive to killing by ShA9 showed significant clinical improvement compared with those receiving only vehicle, according to the study authors.
The investigators noted that their trial was of short duration, included a small cohort, and was limited to only adults with moderate to severe AD who were selected based on positive S aureus colonization.
“Our results support the conclusion that an optimal treatment approach for AD would be one that restores epidermal barrier defects while also suppressing causes of inflammation,” stated the researchers. “The data from the current study show that this new therapeutic approach utilizing commensal microbes to protect the skin is safe over a 7-day period.”
Disclosure: Two of the authors are co-inventors of technology related to the bacterial antimicrobial peptides discussed in the study, and one of the authors is affiliated with industry.
Nakatsuji T, Hata TR, Tong Y, et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat Med. Published online February 22, 2021. doi:10.1038/s41591-021-01256-2