Clinical efficacy of fecal microbial transplantation treatment in adults with moderate-to-severe atopic dermatitis

Jacob Mashiah, Tal Karady, Naomi Fliss-Isakov, Eli Sprecher, Dan Slodownik, Ofir Artzi, Liat Samuelov, Eran Ellenbogen, Anastasia Godneva, Eran Segal, Nitsan Maharshak, Jacob Mashiah, Tal Karady, Naomi Fliss-Isakov, Eli Sprecher, Dan Slodownik, Ofir Artzi, Liat Samuelov, Eran Ellenbogen, Anastasia Godneva, Eran Segal, Nitsan Maharshak

Abstract

Background: Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation.

Methods: We performed the first in-human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1-8 months after the last FMT.

Results: Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4-12 (before and 2 weeks after 4 times of FMT) (59.2 ± 34.9%, Wilcoxon p = .011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5 ± 8.4%, Wilcoxon p = .018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow-up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT. Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow-up period.

Conclusions: FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results.

Keywords: atopic dermatitis; fecal microbial transplantation.

Conflict of interest statement

The authors declare that there are no conflict of interests.

© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Study design: Placebo and FMT schedule. FMT, fecal microbiota transplantation
Figure 2
Figure 2
Changes in patients' SCORAD measurements across study time according to placebo treatments and FMTs. Black line represents the average SCORAD of eligible patients. Vertical line indicates placebo treatments and FMTs. FMT, fecal microbiota transplantation; SCORAD, Scoring Atopic Dermatitis
Figure 3
Figure 3
Pictures of patients 7, 11, 12. All A: Pictures taken at Week 4 (after 2 placebo transplantations and before the FMT treatment). All B: Pictures taken at Week 12 (2 weeks after 4 sessions of FMT). FMT, fecal microbiota transplantation
Figure 4
Figure 4
Measurements change in long‐term follow‐up patients. Patients 2 and 11 SCORAD across time by weeks from the beginning of the study. Vertical lines indicate placebo treatments and FMTs. FMT, fecal microbiota transplantation; SCORAD, Scoring Atopic Dermatitis
Figure 5
Figure 5
Patient samples become similar to donor samples following FMT. t‐SNE (t‐distributed stochastic neighbor embedding) analysis based on sample dissimilarity matrix of patients with available pre‐FMT and post‐FMT samples (N = 8) and donors' samples (N = 3), showing shift of patient samples towards their donor's cluster. Arrows demonstrate the path from baseline samples (square markers), through placebo samples (diamond markers) to post‐FMT samples (circle markers). Color scale matches the patient's main donor. Empty ellipses encompass the donors' samples and filled ellipses encompass patient post‐FMT samples. FMT, fecal microbiota transplantation
Figure 6
Figure 6
Correlation between clinical improvement and similarity in bacterial strains of patients and donors following FMT. Dots correspond to individual patient samples, plotted by their dissimilarity to their donor (x‐axis) versus the reduction of the SCORAD score from baseline (Week 4) at the time of the sample (y‐axis). Arrows demonstrate the path from placebo samples (diamond shape markers) to post‐FMT samples. Ellipse encompass patient post‐FMT samples. FMT, fecal microbiota transplantation

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