Metabolomics: An Emerging Approach to Understand Pathogenesis and to Assess Diagnosis and Response to Treatment in Spondyloarthritis

Rizzo, Carla; Camarda, Federica; Donzella, Denise; Barbera, Lidia La; Guggino, Giuliana

doi:10.3390/cells11030549

Cited by 8 publications

(7 citation statements)

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“…Studies on metabolomics have gained attention in recent years. This has relevance to understanding pathogenesis, diagnosis and response to treatment in AS [60].…”

Section: Metabolomicsmentioning

confidence: 99%

Ankylosing Spondylitis Pathogenesis and Pathophysiology

Alexander¹

2023

Ankylosing Spondylitis - Recent Concepts

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The pathogenesis and pathophysiology of Ankylosing Spondylitis (AS) is complex and remains only partially understood. Contributory genes including a variety of HLA-B27 subset genes and many other non-HLA genes are implicated in the literature. Novel genes and gene–gene interactions being a continuously evolving area of AS research. Dysregulation of the enteric microbiome with a corresponding aberrant immunological response is recognised in research. Certain infectious agents are thought to play a role. A variety of other influences including environmental exposures, dietary and lifestyle factors and sex hormones appear to play a role in AS pathogenesis. There is emerging evidence that that pathophysiological response in AS is an elaborate combination of both autoinflammatory and autoimmune components, however the IL-17/IL-23 pathway remains the major pathway in AS according to studies to date. The specific mechanisms that lead to characteristic clinical features of AS including sacroiliitis, spondylitis, ankylosis, uveitis and other extra articular manifestations remain occult. Further research to establish these is ongoing.

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“…Studies on metabolomics have gained attention in recent years. This has relevance to understanding pathogenesis, diagnosis and response to treatment in AS [60].…”

Section: Metabolomicsmentioning

confidence: 99%

Ankylosing Spondylitis Pathogenesis and Pathophysiology

Alexander¹

2023

Ankylosing Spondylitis - Recent Concepts

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“…Algumas proteínas podem estar envolvidas como claudina 1, claudina 4, zônula occludens, ocludina e VE-caderina, o que resulta no comprometimento das funções de barreira epitelial e endotelial do intestino, levando ao aumento dos níveis séricos de produtos bacterianos, que estão relacionados à inflamação na Espondilite Anquilosante (EA). As interações destas com células imunes, como a célula linfoide inata tipo 3 (ILC3), contribuem para a produção de IL-23, uma citocina fundamental na patogênese dessa doença (RIZZO et al, 2022).…”

Section: Revisão Sistemáticaunclassified

“…Estudo metabolômico, que consiste na identificação de pequenas moléculas (metabólitos) no sistema imunológico, identificou que a diminuição de colina (vitamina B8) promove deposição ectópica de gordura em pacientes com EA, bem como a diminuição da 25-hidroxivitamina D3-peroxilactona, um metabólito de 25(OH)D3 produzido no rim. Outro estudo averiguou que ácidos graxos de cadeia curta (AGCCs) desempenham diversos papéis funcionais na formação do sistema imunológico, regulando as funções de várias células imunes, como macrófagos, células dendríticas, células NKT, células T helper 1 (Th1) e células T reguladoras (Tregs), inibindo a histona desacetilase (HORTA-BAAS; SANDOVAL-CABRERA; ROMERO-FIGUEROA, 2021;RIZZO et al, 2022).…”

Section: Revisão Sistemáticaunclassified

“…Ainda, os níveis plasmáticos de betaína, metionina e N-acetil glicoproteína (NAG) foram aumentados, no qual tanto a betaína quanto a metionina estão implicadas na produção de metionina encefalina (MENK), um regulador da resposta imune. O NAG é conhecido desempenha papel na promoção da acetilação de glicoproteínas, sendo este um processo fundamental para o reconhecimento dos glóbulos brancos, em que seu aumento pode ser responsável pelas alterações dos leucócitos na EA (RIZZO et al, 2022).…”

Section: Revisão Sistemáticaunclassified

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Relação Das Disbioses Da Microbiota Intestinal Nas Doenças Reumáticas Inflamatórias Crônicas

Medeiros¹,

Medeiros²,

Nóbrega³

et al. 2022

TeS

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2017 e abril de 2022, com texto completo (full-text) e em língua inglesa. A amostra final foi composta por 10 publicações. Resultados: Há uma relação entre as disbioses da microbiota intestinal e o surgimento ou agravamento das doenças reumáticas inflamatórias crônicas (DRC). Os mecanismos imunológicos dependem dos patógenos desencadeantes, da falta ou excesso de algumas substâncias. Conclusão: A fisiopatologia das DRC com a microbiota não está completamente elucidada, necessitando de mais estudos. A desregulação da microbiota intestinal pode ser diminuída com o auxílio da mudança da alimentação, uso de probióticos e diminuição do uso crônico de antibióticos que atuam na flora.

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“…Previous studies have demonstrated distinct fecal (12) and serum metabolomic signatures in PsA compared with both rheumatoid arthritis (RA) and healthy individuals (13,14), which correlated to specific cytokines and clinical features. Hence, assessment of intestinal permeability and metabolic profiling of biofluids has an emergent role in exploring the contribution of host-microbiota interactions to the pathogenesis and treatment response of immune-mediated arthritis (15). The lactuloseto-mannitol ratio (LMR) assay is an established test for evaluating gut barrier integrity, whereas 1 H nuclear magnetic resonance (NMR) is a high-throughput, reproducible tool for "global metabolomic profiling," assessing a broad range of host and microbial metabolites across a range of biofluids.…”

Section: Introductionmentioning

confidence: 99%

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

Kragsnaes,

Miguens Blanco,

Mullish

et al. 2023

ACR Open Rheumatology

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ObjectiveWe investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate‐treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).MethodsThis exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate‐to‐high peripheral PsA disease activity, despite at least 3 months of methotrexate‐treatment, were included in a 26‐week, double‐blind, 1:1 randomized, sham‐controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose‐to‐mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance.ResultsTrial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017‐0.33]) vs. 0.012 [0‐0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N‐acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).ConclusionIntestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

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Metabolomics: An Emerging Approach to Understand Pathogenesis and to Assess Diagnosis and Response to Treatment in Spondyloarthritis

Cited by 8 publications

References 61 publications

Ankylosing Spondylitis Pathogenesis and Pathophysiology

Ankylosing Spondylitis Pathogenesis and Pathophysiology

Relação Das Disbioses Da Microbiota Intestinal Nas Doenças Reumáticas Inflamatórias Crônicas

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

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