The Effects of Brodalumab on the Fungal Microbiome in Patients with Psoriasis

Abstract

The gut microbiota plays a critical role in immune system function, with dysbiosis linked to systemic inflammation, contributing to conditions like psoriasis and depression. Although biological treatments for severe psoriasis are known to impact gut bacteria, less is understood about their effects on fungi. This study aims to investigate fungal gut microbiota changes in psoriasis patients transitioning from TNF-α inhibitors to brodalumab. Fecal samples from 20 patients were analyzed using Illumina MiSeq sequencing of the ITS2 region of 18S rRNA. Microbial diversity was assessed through Bray-Curtis dissimilarity and the Shannon-Wiener index. Clinical outcomes were measured using clinical scores for psoriasis and depression severity, with statistical analysis performed via Wilcoxon signed-rank tests and PERMANOVA. Results showed that Ascomycota was the dominant fungal phylum in both treatment groups, with Saccharomyces, Penicillium, Candida, and Debaryomyces as prevalent genera. No significant changes occurred at the phylum level after switching to brodalumab, though minor genome-level variations were observed. Beta diversity analysis highlighted inter-patient variability, with no significant correlation between fungal composition and clinical outcomes. Despite improved clinical scores, the fungal gut microbiota remained largely stable, suggesting that brodalumab does not significantly alter fungal communities in psoriasis patients. Further research is needed for a comprehensive understanding.

Keywords: TNF-alpha inhibitors; brodalumab; fungi; gut microbiome; psoriasis.

Figure 1

The bar chart presents the composition of the gut microbiota on the phylum level before (TNF) and after (B) the switch to brodalumab. Each number represents one patient (p(n)). Each bar is a sample. The y-axis represents the relative abundance of phyla given as OTU composition. Five subjects did not submit samples after the switch, thus excluding them from the comparative analysis (total of 14 patients remained in the final analysis).

Figure 2

The bar chart presents the composition of the gut microbiota on the genus level before (TNF) and after (B) the switch to brodalumab. Each number represents one patient (p(n)). Each bar is a sample. The y-axis represents the relative abundance of phyla given as OTU composition.

Figure 3

PCoA at the genus (a) and phylum (b) level. Patients are represented as specific colors, while the condition before the switch (TNF) is represented as a triangle and the condition after the switch (B) is represented as a circle. The distances between points (shapes) reflect the dissimilarity between microbial communities.

Figure 4

Heat map of the beta diversity of fungi phyla. Red represents a value of 1, high dissimilarity between samples; blue represents a value of 0, low dissimilarity between samples.

Figure 5

Violin plot showing the distributions of the Shannon–Wiener diversity indices across treatment groups. The pink violin represents diversity indices from patients before treatment (TNF), while the green violin represents diversity indices after treatment (B).