Hyperproliferation is the main driver of metabolomic changes in psoriasis lesional skin

Pohla, Liis; Ottas, Aigar; Kaldvee, Bret; Abram, Kristi; Soomets, Ursel; Zilmer, Mihkel; Reemann, Paula; Jaks, Viljar; Kingo, Külli

doi:10.1038/s41598-020-59996-z

Cited by 44 publications

(61 citation statements)

References 39 publications

(48 reference statements)

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“…Data were confirmed by an unsupervised and supervised analysis. Some of these variations are consistent with some previous studies on either sera or lesional skin samples from psoriasis patients 19 , 20 . However, we did not take into account some potential confounding factors (e.g., dietary habits), and we cannot rule out that patients with more severe psoriasis might show a different metabolic profile.…”

Section: Discussionsupporting

confidence: 91%

Integrated metabolomic analysis and cytokine profiling define clusters of immuno-metabolic correlation in new-onset psoriasis

Tarentini

Odorici

Righi

et al. 2021

Sci Rep

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The association between the metabolic profile and inflammatory cytokines in psoriasis is poorly understood. We analyzed the metabolic and cytokine/chemokine profiles in serum and skin from patients with new-onset psoriasis and healthy subjects (n = 7/group) by HR-MAS NMR and Bio-Plex immunoassay. Immuno-metabolic correlation matrix was analyzed in skin and serum to identify a potential immune-metabolic signature. Metabolomics analysis showed a significant increase in ascorbate and a decrease in scyllo-inositol, and a trend towards an increase in eight other metabolites in psoriatic skin. In serum, there was a significant increase of dimethylglycine and isoleucine. In parallel, psoriatic skin exhibited an increase of early inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β) and correlation analysis highlighted some major clusters of immune-metabolic correlations. A cluster comprising scyllo-inositol and lysine showed correlations with T-cell cytokines; a cluster comprising serine and taurine showed a negative correlation with early inflammatory cytokines (IL-6, G-CSF, CCL3). A strong positive correlation was enlightened between glutathione and inflammatory cytokines/angiogenesis promoters of psoriasis. The integration of metabolic and immune data indicated a molecular signature constituted by IL-6, IL1-ra, DMG, CCL4, Ile, Gly and IL-8, which could discriminate patients and healthy subjects and could represent a candidate tool in the diagnosis of new-onset psoriasis.

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Section: Discussionsupporting

confidence: 91%

Integrated metabolomic analysis and cytokine profiling define clusters of immuno-metabolic correlation in new-onset psoriasis

Tarentini

Odorici

Righi

et al. 2021

Sci Rep

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“…Generally, psoriatic disease-related metabolomics studies aim to identify metabolic markers that can be used for Ps and/or PsA diagnosis. While a few studies have examined the metabolite profiles of patients with autoimmune diseases (ADs) [9,10], or immunemediated inflammatory diseases (IMIDs) with no emphasis on Ps or PsA specifically [11], the majority of studies included in this review sought to identify metabolites that were associated with Ps by investigating Ps patients in comparison to healthy volunteers [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Other studies focused on identifying metabolite profiles in Ps patients and correlating them with different measurements of disease activity [13,19,22,28,32,33].…”

Section: The Biological Questionmentioning

confidence: 99%

“…Most studies included in our literature search were non-hypothesis driven and therefore employed an untargeted metabolomics approach [12,[14][15][16][19][20][21][22][23]25,26,[31][32][33]36,41,42]. However, there were several studies that analyzed specific metabolites using a targeted metabolomics approach [9,10,13,18,24,27,28,30,39,40].…”

Section: Experimental Designmentioning

confidence: 99%

Metabolomics Studies in Psoriatic Disease: A Review

et al. 2021

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Metabolomics investigates a broad range of small molecules, allowing researchers to understand disease-related changes downstream of the genome and proteome in response to external environmental stimuli. It is an emerging technology that holds promise in identifying biomarkers and informing the practice of precision medicine. In this review, we summarize the studies that have examined endogenous metabolites in patients with psoriasis and/or psoriatic arthritis using nuclear magnetic resonance (NMR) or mass spectrometry (MS) and were published through 26 January 2021. A standardized protocol was used for extracting data from full-text articles identified by searching OVID Medline ALL, OVID Embase, OVID Cochrane Central Register of Controlled Trials and BIOSIS Citation Index in Web of Science. Thirty-two studies were identified, investigating various sample matrices and employing a wide variety of methods for each step of the metabolomics workflow. The vast majority of studies identified metabolites, mostly amino acids and lipids that may be associated with psoriasis diagnosis and activity. Further exploration is needed to identify and validate metabolomic biomarkers that can accurately and reliably predict which psoriasis patients will develop psoriatic arthritis, differentiate psoriatic arthritis patients from patients with other inflammatory arthritides and measure psoriatic arthritis activity.

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“…Glucose metabolism, amino acid metabolism, and lipid metabolism have been shown to be significantly changed in psoriasis patients ( Zeng et al, 2017 ; Zhu and Thompson, 2019 ). The roles of metabolic regulation of cell proliferation and apoptosis are considered to be key to unregulated keratinocyte pathogenesis in psoriasis ( Luo et al, 2020 ; Pohla et al, 2020 ). In addition, it is well known that the chronic inflammatory features of psoriasis, the associated characteristics of metabolic syndrome with psoriasis, and even the diet-related pathogenesis mechanism of psoriasis all indicate the importance of metabolism in the disease ( Wolters, 2005 ; Gisondi et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Microbiome and Metabolome Analyses Reveal Novel Interplay Between the Skin Microbiota and Plasma Metabolites in Psoriasis

Chen

He²,

et al. 2021

Front. Microbiol.

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Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. There is still no effective approach for the clinical treatment of psoriasis. This is largely due to the lack of understanding of the pathological mechanism. Here, we comprehensively characterized the skin microbiome and plasma metabolome alterations of psoriasis patients. We observed that some pathogenic bacteria, including Vibrio, were significantly increased in psoriasis patients. The metabolomics results showed alterations in some metabolic pathways, especially pathways for lipid metabolism. In addition, microbiome-specific metabolites, including bile acids and kynurenine, were significantly changed. Correlation analysis revealed the interplay between the skin microbiota and plasma metabolites, especially between Vibrio and several lipids. Our results provide new evidence for the interplay between the skin microbiome and plasma metabolites, which is dramatically disrupted in psoriasis patients. This study also revealed the mechanism underlying the pathogenesis of psoriasis.

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Hyperproliferation is the main driver of metabolomic changes in psoriasis lesional skin

Abstract: Materials and Methods ethics approval. This study was approved by the Research Ethics Committee of the University of Tartu. Permission number 245/M-18. The Declaration of Helsinki protocols were followed and patients gave their informed, written consent.

Cited by 44 publications

References 39 publications

Integrated metabolomic analysis and cytokine profiling define clusters of immuno-metabolic correlation in new-onset psoriasis

Integrated metabolomic analysis and cytokine profiling define clusters of immuno-metabolic correlation in new-onset psoriasis

Metabolomics Studies in Psoriatic Disease: A Review

Microbiome and Metabolome Analyses Reveal Novel Interplay Between the Skin Microbiota and Plasma Metabolites in Psoriasis

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