Abstract
Immunotherapy could change the complex host-microbial interactions. We aimed to investigate the dynamics of gut microbiome in response to secukinumab [an interleukin (IL)-17 inhibitor] and ustekinumab (an IL-12/23 inhibitor) therapy and its association with treatment response in psoriasis. This observational, longitudinal study collected a total of 114 fecal samples from 12 healthy controls and 34 patients with psoriasis at baseline and 3 and 6months after secukinumab (n = 24) or ustekinumab treatment (n = 10) and gut microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA. Secukinumab treatment causes more profound alterations in gut microbiome, including increases in the relative abundance of phylum Proteobacteria and decreases in Bacteroidetes and Firmicutes, than ustekinumab treatment. The relative abundance of family Pseudomonadaceae, family Enterobacteriaceae and order Pseudomonadales also increased significantly following secukinumab therapy. In contrast, there was no significant change in gut microbiome composition following ustekinumab treatment, and only genus Coprococcus significantly increased after 6months of ustekinumab therapy. Moreover, we observed significant differences in baseline gut microbiome between responders and non-responders to secukinumab treatment. These results indicate that gut microbiome is altered differently after anti-IL17 and anti-IL12/23 treatment. Secukinumab (anti-IL17) therapy is associated with distinct and more profound gut microbiome shifts than ustekinumab therapy (anti-IL 12/23) in patients with psoriasis. Moreover, gut microbiome would serve as potential biomarkers of response to secukinumab treatment.
Published Version
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