Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial

Loesche, Michael A.; Farahi, Kamyar; Capone, Kimberly; Fakharzadeh, Steven; Blauvelt, Andrew; Duffin, Kristina Callis; DePrimo, Samuel E.; Muñoz‐Elías, Ernesto J.; Brodmerkel, Carrie; Dasgupta, B.; Chévrier, Marc; Smith, Kevin S.; Horwinski, Joseph; Tyldsley, Amanda S.; Grice, Elizabeth A.

doi:10.1016/j.jid.2018.03.1501

Cited by 52 publications

(50 citation statements)

References 28 publications

(47 reference statements)

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“…30,31,65 Antimicrobial peptides (AMPs), Toll-like receptors (TLRs) and peptidoglycan recognition proteins (PGRPs) can also modulate bacterial colonization and function. 50 In terms of psoriasis, modulation of the cutaneous microbiome may be possible via (1) UV radiation, (2) anti-interleukin (IL)-17/23 systemic therapy, 66 (3) microbial regulation of angiogenesis, 67 (4) translocation or modulation of gut bacteria, [68][69][70][71][72] (5) modulation of hormone production, 73 (6) altered AMP/ TLR expression and/or direct application of protective bacterial strains. 8,64 PRL, prolactin; TNF, tumour necrosis factor; Treg, regulatory T cell.…”

Section: Discussionmentioning

confidence: 99%

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis

et al. 2019

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Summary Background The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. Objectives To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. Methods Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI‐TOF) in a prospective study. Results Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. Conclusions Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis

et al. 2019

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“…19,20 The aetiology of psoriasis remains elusive but for decades it has been a wellknown fact that there is a relationship between streptococcal pharyngitis and a particular clinical form of psoriasis, so-called guttate psoriasis. 21 Recently, several studies have been conducted that focus on skin microbiome alterations and their connection with psoriasis [22][23][24][25][26][27] and atopic dermatitis, 28 although less attention has been focused on the potential role of gut microbiota dysbiosis in the pathogenesis of the disease. 29 Our hypothesis is that the intestinal microbiota dysbiosis may play a key role in the development of psoriatic disease due to an aberrant inflammatory response that can be connected with the skin.…”

Section: What Does This Study Add?mentioning

confidence: 99%

Gut microbiota dysbiosis in a cohort of patients with psoriasis

et al. 2019

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Summary Background There is increasing evidence of the key role that the gut microbiota plays in inflammatory diseases. Objectives To identify differences in the faecal microbial composition of patients with psoriasis compared with healthy individuals in order to unravel the microbiota profiling in this autoimmune disease. Methods 16S rRNA gene sequencing and bioinformatic analyses were performed with the total DNA extracted from the faecal microbiota of 19 patients with psoriasis and 20 healthy individuals from the same geographic location. Results Gut microbiota composition of patients with psoriasis displayed a lower diversity and different relative abundance of certain bacterial taxa compared with healthy individuals. Conclusions The gut microbiota profile of patients with psoriasis displayed a clear dysbiosis that can be targeted for microbiome‐based therapeutic approaches. What's already known about this topic? Psoriasis is a chronic inflammatory immune‐mediated skin disease, the aetiology of which remains unclear. The human microbiota is a complex microbial community that inhabits our body and has been related with the maintenance of a healthy status. Several studies have focused on the skin microbiome and its connection with psoriasis although less attention has been focused on the potential role of the gut microbiota in psoriatic disease. What does this study add? This study unravels the gut microbiome dysbiosis present in a cohort of patients with psoriasis, compared with a healthy control group from the same geographical location. This study shows a lower bacterial diversity and different relative abundance of certain bacterial taxa in patients with psoriasis. We gain knowledge and insight into the microbiome alterations in psoriatic disease, opening new avenues for therapeutic approaches to reshape the human microbiome towards a healthy status.

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“…Bearing in mind that the use of biologics is associated with changes in the composition of both the cutaneous [78,85] and gastrointestinal microbiomes [86], it is at least conceivable that biomarkers of treatment response may be identified in future metagenomic studies. Moreover, there is emerging evidence that chronic inflammatory skin disorders may be associated with specific perturbations in the gastrointestinal microbiome.…”

Section: The Cutaneous And/or Gastrointestinal Microbiomes As a Theramentioning

confidence: 99%

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel

Langan

Recke

Bokor-Billmann

et al. 2020

IJMS

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The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)-also known as acne inversa-a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.scoring and the HS severity index. Whilst the precise incidence and prevalence of HS is unclear [8], due partly to the diagnostic difficulty associated with HS and the use of both registry data and self-report questionnaires [9]. Garg et al. reported a prevalence of 0.1% in a US-based population analysis, leading the authors to conclude that HS is an uncommon but not rare disease, with over-representation in young, female and African American patients [10]. The current multi-modal treatment approach includes the use of intralesional steroids, surgical and laser therapy, topical and systemic medical antimicrobial therapy and biologic treatments [11].Sartorius scoring and the HS severity index. Whilst the precise incidence and prevalence of HS is unclear [8], due partly to the diagnostic difficulty associated with HS and the use of both registry data and self-report questionnaires [9]. Garg et al. reported a prevalence of 0.1% in a US-based population analysis, leading the authors to conclude that HS is an uncommon but not rare disease, with over-representation in young, female and African American patients [10]. The current multi-modal treatment approach includes the use of intralesional steroids, surgical and laser therapy, topical and systemic medical antimicrobial therapy and biologic treatments [11].

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Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial

Cited by 52 publications

References 28 publications

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis

Gut microbiota dysbiosis in a cohort of patients with psoriasis

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa—Light at the End of the Microbiological Tunnel

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