Successful secukinumab therapy in plaque psoriasis is associated with altered gut microbiota and related functional changes

Abstract

IntroductionThe 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.MethodsIn 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.ResultsWe 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.DiscussionIt seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.

Combined analysis of metabolomics and 16S rRNA sequencing for ankylosing spondylitis patients before and after secukinumab therapy

“…possibly attributed to the anti-inflammatory effects of the medication, which may have altered the gut microenvironment and improve microbial diversity. 14 It is worth noting that commonly used therapies, such as NSAIDs, methotrexate, leflunomide, and glucocorticoids, can inhibit the growth of specific gut bacteria, leading to gut microbiota diversity decrease. 15,16 The composition of the gut microbiota in AS patients after secukinumab therapy became more similar to that of the HC group.…”

“…2 A link has been confirmed between the severity of subclinical intestinal inflammation and involvement of the sacroiliac joints. 14,17 Moreover, with the administration of secukinumab, these inflammatory changes in the gut may improve further, thereby reducing the risk of developing gastrointestinal symptoms. Since none of the patients in this group had IBD or gastrointestinal symptoms before or after treatment, we are not sure about the impact of secukinumab treatment on the incidence of IBD in AS patients.…”

“…2 The prevalence of AS ranges from 0.1% to 1.4%, predominantly affecting young to middle-aged men, with 90% of patients developing clinical symptoms before the age of 40. 3 The gut, home to a microbial population more numerous than the human body's cells, approximately 10 14 , acts as a "microbial organ". 4 This intricate community metabolizes food components into nutrients, safeguards against pathogenic invasion through the gastrointestinal mucosa, and upholds immune system equilibrium.…”

Interleukins and Psoriasis

“…On the other hand, another study showed that treatment with secukinumab resulted in a more stable gut microbiome homeostasis, with an increase in the abundance of thickwalled bacterial phyla and a decrease in anaplastic bacterial phyla in patients receiving secukinumab. 161 These conflicting results highlight the complexity of the gut microbiota and individual differences among patients, making it challenging to understand the mechanisms behind these paradoxical effects fully. In conclusion, the impact of biologics on gut flora in psoriasis patients is an intriguing area of research.…”

Network pharmacology and gut microbiota insights: unraveling Shenling Baizhu powder’s role in psoriasis treatment

“…Gut microbiota, comprising trillions of microorganisms, significantly influences systemic immunity and inflammation ( Giambra et al, 2023 ; Li et al, 2023 ). Dysbiosis, an imbalance in the gut microbial composition, has been implicated in exacerbating psoriasis ( Buhas et al, 2022 ; Cai et al, 2023 ; Du et al, 2023 ). Alterations in gut microbiota can lead to increased intestinal permeability, allowing bacterial products to enter the circulation and potentially trigger systemic inflammation, which can exacerbate skin lesions.…”