Changes of Gut Microbiome in Adolescent Patients with Chronic Spontaneous Urticaria After Omalizumab Treatment

Abstract

Purpose: Omalizumab is a humanized anti-immunoglobulin (Ig) E monoclonal antibody that is effective in treating some patients with chronic spontaneous urticaria (CSU) who do not respond to antihistamines. Gut microbiome plays a role in the pathogenesis of allergies and autoimmune diseases. Here, we investigated differences in the gut microbiome of adolescent CSU patients before and after omalizumab treatment, which has not been previously reported.

Patients and methods: Ten adolescent CSU patients were given 300 mg omalizumab subcutaneously in three treatments at 4-week intervals. Urticaria Activity Score (UAS7) was applied to evaluate the efficacy of each omalizumab treatment during follow-up. Fecal samples were collected before and 12 weeks after the first treatment. Total DNA of the gut microbiota in all fecal samples were extracted. The 16S rRNA gene-targeted sequencing technology was used for the analysis of the diversity and distribution of gut microbiome, followed by bioinformatics analysis.

Results: UAS7 scores decreased significantly after each treatment compared with the baseline (all P < 0.0001). There were five well-controlled responders and five non-responders after three treatment sessions of omalizumab. The dominant bacteria phyla in all fecal samples were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Alpha diversity analysis showed no significant difference before and after treatment (P > 0.05), whereas beta diversity analysis revealed a significant difference in the bacterial abundance before and after treatment (P < 0.01). The relative abundance of Alphaproteobacteria and Betaproteobacteria at the class level and Burkholderia, Rhodococcus, and Sphingomonas at the genus level decreased significantly after treatment (linear discriminant analysis > 4, P < 0.05). The functional prediction results showed that the dioxin and xylene degradation pathways were more abundant before treatment.

Conclusion: Omalizumab is effective in treating CSU and the abundance of Alphaproteobacteria and Betaproteobacteria was reduced after treatment, which may help improve the treatment outcomes in adolescent CSU patients.

Keywords: 16S rRNA gene-targeted sequencing; adolescent patients; chronic spontaneous urticaria; gut microbiome; omalizumab.

Figure 1

Study flowchart of materials and methods.

Figure 2

Changes in UAS7 at baseline and 4, 8, and 12 weeks after the first omalizumab treatment of CSU patients. (****P < 0.0001).

Figure 3

Venn diagram demonstrating operational taxonomic units common or unique to omalizumab pre-treatment and post-treatment groups.

Figure 4

Differences in alpha diversity between adolescent CSU patients before and after omalizumab treatment. (A) Alpha diversity evaluated according to the observed OTUs indices. (B) Alpha diversity evaluated according to the Chao1 indices. (C) Alpha diversity evaluated according to the Shannon indices. (D) Alpha diversity evaluated according to the Simpson indices.

Figure 5

Gut microbiota composition in patients with CSU before and after treatment. (A) The top 13 taxa in relative abundance at the phylum level; (B) The top 20 taxa in relative abundance at the class level; (C) The top 20 taxa in relative abundance at the order level; (D) The top 20 taxa in relative abundance at family level; (E) The top 20 taxa in relative abundance at the genus level; (F) The top 20 taxa in relative abundance at the species level.

Figure 6

Beta diversity analysis based on PCoA and LEfSe. (A) PCoA of the bacterial community composition before and after treatment. (B) LEfSe analysis of the difference in the bacterial taxa relative abundance. Bacterial with Linear Discriminant Analysis (LDA) scores > 4.0 were considered significantly different.

Figure 7

Differential pathway functional analysis between adolescent patients with CSU before and after omalizumab treatment. *P < 0.05.