Introduction The gut-skin axis (GSA) is crucial for understanding the pathogenesis of inflammatory skin diseases such as psoriasis, which is characterized by specific dysbiotic signatures of both the gut and skin microbiota. Gut dysbiosis may alter skin homeostasis through the GSA and immune signalling networks, involving IL-23 and IL-17 cytokines. Targeting these pro-inflammatory pathways could be one of the therapeutic alternatives for psoriasis, and anti-IL-23 or anti-IL-17 monoclonal antibodies (mAbs) are indeed effective systemic treatments for moderate to severe psoriasis.This study aims to i) evaluate the gut microbiota and its variation in psoriasis patients before, during, and after systemic anti-IL-23 or anti-IL-17 therapy; ii) assess clinical outcomes such as Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Investigators Global Assessment (IGA) at the baseline and during the follow-up visits. Materials & Methods Stool samples were collected from a cohort of informed consent naive psoriatic patients (n = 43) at baseline (T0), after 16 (T16) and 52 (T52) weeks of treatment with anti-IL-23 or anti IL-17 mAbs. Microbial DNA was isolated (QIAmp PowerFecal Pro DNA Kit). Gut microbiota composition was analysed using 16S rDNA sequencing of the V3-V4-V6 hypervariable regions, processed with MicrobAT software and the Ribosomal Project Database (RDP) database, and assessed with MicrobiomeAnalyst for alpha- and beta-diversity. Clinical endpoints were statistically analysed as well. Results Preliminary data confirm an altered Bacillota (formerly Firmicutes)/Bacteroidetes [B(F)/B] ratio at T0, which indicates intestinal dysbiosis. Both the treatments not only improve the condition, but also shift the B(F)/B ratio, increasing species within the Bacteroidetes phylum and enhancing microbiota biodiversity. Besides microbiota changes, both the treatments improve PASI, IGA, and DLQI scores compared to the baseline. Conclusion These results demonstrate a progressive increment in gut biodiversity and a normalization of the ratio of B(F)/B in both the patient groups. This pilot study underscores the potential role of biologics in the GSA homeostasis, as the restoration of gut microbiota may support clinical outcomes in psoriasis treatment. Moreover, multicentric studies and gut microbiota analysis on a larger scale could pave the way to better comprehend the relationship between psoriasis and microbiome and lead to personalized, microbiota-targeted therapeutic strategies.

Effect of anti-IL-17 and anti-IL-23 monoclonal antibodies on gut microbiota in patients with psoriasis: a single centre observational study

Marta Armari
Primo
;
Chiara Maria Teresa Boggio;Edoardo Cammarata;Marta Mellai;Federica Veronese;Paola Savoia;Barbara Azzimonti
Ultimo
2025-01-01

Abstract

Introduction The gut-skin axis (GSA) is crucial for understanding the pathogenesis of inflammatory skin diseases such as psoriasis, which is characterized by specific dysbiotic signatures of both the gut and skin microbiota. Gut dysbiosis may alter skin homeostasis through the GSA and immune signalling networks, involving IL-23 and IL-17 cytokines. Targeting these pro-inflammatory pathways could be one of the therapeutic alternatives for psoriasis, and anti-IL-23 or anti-IL-17 monoclonal antibodies (mAbs) are indeed effective systemic treatments for moderate to severe psoriasis.This study aims to i) evaluate the gut microbiota and its variation in psoriasis patients before, during, and after systemic anti-IL-23 or anti-IL-17 therapy; ii) assess clinical outcomes such as Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Investigators Global Assessment (IGA) at the baseline and during the follow-up visits. Materials & Methods Stool samples were collected from a cohort of informed consent naive psoriatic patients (n = 43) at baseline (T0), after 16 (T16) and 52 (T52) weeks of treatment with anti-IL-23 or anti IL-17 mAbs. Microbial DNA was isolated (QIAmp PowerFecal Pro DNA Kit). Gut microbiota composition was analysed using 16S rDNA sequencing of the V3-V4-V6 hypervariable regions, processed with MicrobAT software and the Ribosomal Project Database (RDP) database, and assessed with MicrobiomeAnalyst for alpha- and beta-diversity. Clinical endpoints were statistically analysed as well. Results Preliminary data confirm an altered Bacillota (formerly Firmicutes)/Bacteroidetes [B(F)/B] ratio at T0, which indicates intestinal dysbiosis. Both the treatments not only improve the condition, but also shift the B(F)/B ratio, increasing species within the Bacteroidetes phylum and enhancing microbiota biodiversity. Besides microbiota changes, both the treatments improve PASI, IGA, and DLQI scores compared to the baseline. Conclusion These results demonstrate a progressive increment in gut biodiversity and a normalization of the ratio of B(F)/B in both the patient groups. This pilot study underscores the potential role of biologics in the GSA homeostasis, as the restoration of gut microbiota may support clinical outcomes in psoriasis treatment. Moreover, multicentric studies and gut microbiota analysis on a larger scale could pave the way to better comprehend the relationship between psoriasis and microbiome and lead to personalized, microbiota-targeted therapeutic strategies.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/211762
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