Groundbreaking research reveals how gut microbiome changes during biologic therapy are associated with treatment response in psoriasis patients.
For millions living with psoriasis, the relentless cycle of inflamed, scaly skin patches is more than a surface-level concern. It's a chronic, systemic inflammatory battle raging within.
For decades, treatment has focused on calming the overactive immune response in the skin itself. But groundbreaking research is now shifting the spotlight to an unexpected arena: the vast, hidden ecosystem of our gut.
Scientists are uncovering that the trillions of microbes residing in our intestines play a pivotal role in the onset and progression of psoriasis. This communication network, dubbed the "gut-skin axis," allows our gut bacteria to influence distant organ health, including our skin.
Even more revolutionary is the discovery that effective psoriasis treatments, like the biologics Secukinumab and Ustekinumab, don't just target the skin—they actively reshape this inner microbial universe. Recent studies reveal that these therapies perturb the gut microbiome in distinct ways, and these changes are closely linked to their success in clearing psoriatic plaques, opening up exciting new frontiers for personalized medicine.
The gut microbiome is now recognized as an active player in psoriasis pathogenesis and treatment response, not just a passive bystander.
The intricate, two-way communication between gut microorganisms and skin health
The gut microbiome is essential for the development and regulation of our immune homeostasis. It interacts with both innate and adaptive immune components, helping to distinguish between friendly bacteria and potential threats.
In psoriatic patients, alterations in the gut microbiome can trigger both systemic and localized inflammation 7 . Dysbiosis can lead to regulatory T cell (Treg) dysfunction and the unwanted activation of pro-inflammatory Th17 cells, a key driver of psoriatic inflammation 7 .
Gut bacteria ferment dietary fiber to produce short-chain fatty acids (SCFAs)—such as butyrate, propionate, and acetate. These compounds are crucial for maintaining an intact intestinal barrier, regulating inflammation, and supporting overall immune function 2 7 .
Notably, patients with psoriasis often have reduced levels of SCFA-producing bacteria like Faecalibacterium and Akkermansia 5 . This deficiency can contribute to a "leaky gut," where the intestinal barrier becomes permeable, allowing bacterial fragments to enter the bloodstream and promote systemic inflammation 5 .
Patients with psoriasis typically show distinct gut microbiome profiles compared to healthy individuals, characterized by reduced diversity and altered abundance of key bacterial taxa.
Different mechanisms of action lead to distinct microbiome perturbations
Secukinumab is a biologic drug that directly inhibits interleukin-17A (IL-17A), a central cytokine in the pathogenesis of psoriasis 4 . By binding to IL-17A, it prevents this inflammatory signal from reaching its receptor on cells, thereby reducing the inflammation that leads to skin cell overproduction.
Directly binds and neutralizes IL-17A cytokine
IL-17 signaling pathway
Increases beneficial SCFA-producing bacteria
Ustekinumab takes a different approach. It targets interleukin-23 (IL-23), a cytokine that is upstream of IL-17A . IL-23 is crucial for the survival and proliferation of Th17 cells. By inhibiting IL-23, Ustekinumab indirectly dampens the entire Th17 pathway, including the production of IL-17A.
Binds p40 subunit shared by IL-12 and IL-23
IL-23/Th17 axis
Different microbial shift pattern compared to Secukinumab
Direct IL-17A inhibition
IL-23/Th17 pathway inhibition
A pivotal 2025 study provides clear evidence of Secukinumab's effect on the gut microbiome
The researchers recruited 110 patients with moderate-to-severe plaque psoriasis and 60 healthy controls. The psoriasis patients were randomly assigned to provide fecal samples at two key time points:
Samples collected before any Secukinumab was administered.
Samples collected after 24 weeks of Secukinumab therapy.
The scientists then used PacBio Full-Length 16S rRNA Gene Sequencing, an advanced technique that provides a highly accurate census of the bacterial species present in each sample. They analyzed changes in both microbial diversity and the abundance of specific bacterial groups, correlating these shifts with clinical improvements in psoriasis severity (measured by PASI scores) 4 .
The study found that while Secukinumab rapidly improved skin symptoms, the gut microbiome underwent a more gradual transformation. After 24 weeks of treatment, the microbial composition in the treated group had significantly changed compared to both the pre-treatment and healthy control groups.
The results were not about simply restoring the microbiome to a "healthy" state, but about inducing a unique, treatment-associated shift. The analysis revealed a distinct signature in Secukinumab-treated patients, characterized by an increased abundance of beneficial genera like Agathobacter and Anaerobutyricum, which are known SCFA producers, and a decreased presence of Bacteroides and Phocaeicola 4 . This suggests that part of Secukinumab's therapeutic effect may be linked to its ability to foster a gut environment that is less inflammatory and more conducive to immune regulation.
| Bacterial Taxon | Change | Significance |
|---|---|---|
| Agathobacter | Increased | SCFA production |
| Anaerobutyricum | Increased | Butyrate production |
| Bacteroides | Decreased | Community structure shift |
| Phocaeicola | Decreased | IL-17A inhibition response |
Advanced technologies enabling breakthroughs in gut microbiome analysis
| Tool or Reagent | Function in Research | Real-World Example |
|---|---|---|
| 16S rRNA Gene Sequencing | Profiles bacterial composition by sequencing a conserved genetic region. | Used in the Secukinumab study 4 and skin microbiome studies . |
| Shotgun Metagenomics | Sequences all genetic material in a sample, allowing functional potential analysis. | Mentioned as a method for in-depth microbial characterization 2 . |
| PacBio Long-Read Sequencing | A type of sequencing that provides longer, more accurate reads for better species identification. | Employed for "PacBio Full-Length Diversity Sequencing" in the Secukinumab study 4 . |
| LEfSe (LDA Effect Size) Analysis | A statistical method that identifies biomarkers (specific taxa) that explain differences between groups. | Used to find differentially abundant bacteria after Secukinumab treatment 4 . |
| PICRUSt2 (Software) | Predicts the functional capabilities of a microbiome based on its 16S rRNA gene sequencing data. | Used to infer functional changes in the skin microbiome after IL-17A therapy . |
Advanced sequencing methods allow researchers to identify and quantify microbial species with unprecedented accuracy.
Sophisticated computational tools analyze massive datasets to identify patterns and relationships in microbial communities.
Standardized protocols for sample collection, DNA extraction, and quality control ensure reliable and reproducible results.
The gut microbiome as an active player and predictor in treatment outcomes
The discovery that distinct therapies cause distinct microbial shifts opens up a new dimension in managing psoriasis. The gut microbiome is no longer a passive bystander but an active player and potential predictor in treatment outcomes. This understanding paves the way for a more personalized, effective approach to psoriasis care.
Future research is poised to answer critical questions: Can we analyze a patient's gut microbiome before treatment to predict whether they will respond better to Secukinumab or Ustekinumab? Can probiotics, prebiotics, or even fecal microbiota transplantation (FMT) be strategically used to support these therapies and improve outcomes?
Studies have already shown that probiotic supplementation, specifically with strains like Bifidobacterium longum and Lactobacillus rhamnosus, can reduce psoriasis severity and lower the risk of relapse 5 .
Research confirms that therapies like Ustekinumab also change the skin microbiome, adding another layer to this complex interaction .
While the field is developing rapidly, the message is clear: achieving clear skin in psoriasis is a whole-body endeavor. By treating the unseen ecosystem within our gut, we are unlocking powerful new strategies to heal the skin visible to the world.
The future of psoriasis treatment lies in understanding individual microbiome profiles to tailor therapies for maximum efficacy and minimal side effects.