Gut Microbiome in Psoriasis is Perturbed Differently During Secukinumab and Ustekinumab Therapy and Associated with Response to Treatment
Background and Objective
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 6 months 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 6 months 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.
The authors would like to thank Dr. Yu-Lun Kuo at BIOTOOLS Co., Ltd., in Taiwan for the kind support in the analysis of NGS data. All authors have significantly contributed to the manuscript and all agree with its contents. Authors do not have any relevant financial interests in the findings from this manuscript.
Compliance with Ethical Standards
This study was supported by the National Taiwan University Hospital, Hsinchu Branch (106-HCH028 and 107-HCH009) and the Ministry of Science and Technology, Taiwan (formerly, the National Science Council; Grant Numbers, MOST 107-2314-B-002-259-MY3).
Conflict of interest
Dr. Tsen-Fang Tsai has conducted clinical trials or received honoraria for serving as a consultant for Abbvie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galderma, GSK, Janssen-Cilag, Leo Pharma, Merck-Serono, Novartis International AG, and Pfizer Inc. Dr. Hsien-Yi Chiu have received speaking fees from AbbVie, Eli-Lilly, Novartis Pharmaceuticals Corporation, Janssen-Cilag Pharmaceutica, and Pfizer Limited. Other authors have no conflicts of interest to declare.
Ethics approval and informed consent
The study protocol was reviewed and approved by the local Institutional Review Board of the National Taiwan University Hospital, Hsinchu branch (105-069-E) and informed consent had been obtained from each patient.
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