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Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Successful secukinumab therapy in plaque psoriasis is associated with altered gut microbiota and related functional
Xueshan Du1, Cong Yan1, Shuzhen Kong1
1Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Introduction:
The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients.
Methods:
In our study, we compared the fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively, by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was first used to characterize bacterial gut microbial communities and related functional changes in the AT group.
Results:
We found that the diversity and structure of the microbial community in the AT group were significantly changed compared to those in the BT group and the H group. The AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of the gut microbiome with functional alteration. There were different KEGG pathways, such as the downregulated cardiovascular diseases pathway and the upregulated infectious diseases in the AT group. By metagenomic analysis, the metabolic functional pathway was changed after secukinumab therapy.
Discussion:
It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.
Insights
Successful secukinumab treatment for psoriasis alters gut microbiota, increasing Firmicutes and Ruminococcaceae while decreasing Bacteroidota. This indicates a more stable gut microbiome with functional changes, potentially aiding in predicting treatment efficacy.
Area of Science:
- Microbiome research
- Immunodermatology
- Pharmacogenomics
Background:
- Psoriasis pathogenesis is linked to gut microbiome dysbiosis.
- Secukinumab, an IL-17 inhibitor, shows efficacy in psoriasis treatment.
- The impact of secukinumab on gut microbiota remains largely unknown.
Purpose of the Study:
- To investigate gut microbiota alterations in psoriatic patients after successful secukinumab therapy.
- To characterize functional changes in the gut microbiome post-treatment.
- To explore the relationship between gut microbiota and secukinumab efficacy.
Main Methods:
- 16S rRNA sequencing to profile fecal microbiome.
- Shotgun metagenomic sequencing for bacterial communities and functions.
- Comparison between treated (AT), untreated (BT) psoriatic patients, and healthy controls (H).
Main Results:
- Secukinumab treatment significantly altered microbial diversity and structure.
- Increased Firmicutes and Ruminococcaceae, with reduced Bacteroidota (elevated F/B ratio) observed in AT group.
- Functional analysis revealed altered KEGG pathways, including downregulated cardiovascular diseases and upregulated infectious diseases, indicating improved gut homeostasis.
Conclusions:
- Secukinumab therapy induces significant gut microbiota and functional shifts in psoriatic patients.
- Gut microbiome analysis may help predict secukinumab efficacy and potential risks.
- Further research into microbiome-targeted therapies for psoriasis is warranted.
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