Altered kynurenine pathway metabolism in patients with ankylosing spondylitis

Onmaz, Duygu Eryavuz; Sivrikaya, Abdullah; Işık, Kevser; Abuşoğlu, Sedat; Gezer, İlknur Albayrak; Yerlikaya, Fatma Hümeyra; Abuşoğlu, Gülsüm; Ünlü, Ali; Tezcan, Dilek

doi:10.1016/j.intimp.2021.108018

Cited by 19 publications

(46 citation statements)

References 40 publications

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“…The serum kynurenine-to-tryptophan ratio, proposed as a metric of immune activation 46,47 , was positively correlated with CRP (Fig. 3c), in line with a previous study which found anti-TNF-α therapy to be effective at reducing both clinical markers in SpA 48 .…”

Section: Resultssupporting

confidence: 90%

“…We also found Veillonella abundances, which were elevated in our cohorts, to be negatively correlated with circulating tryptophan, which had a weakly negative correlation with CRP. The serum kynurenine-to-tryptophan ratio, proposed as a metric of immune activation 46,47 , was positively correlated with CRP (Fig. 3c), in line with a previous study which found anti-TNF-α therapy to be effective at reducing both clinical markers in SpA 48 .…”

Section: Resultssupporting

confidence: 90%

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Spondyloarthritis, acute anterior uveitis, and Crohn’s disease have both shared and distinct gut microbiota

Essex

Rodriguez

Rademacher

et al. 2022

Preprint

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Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with non-musculoskeletal inflammatory disorders such as acute anterior uveitis and Crohn’s disease. The gut microbiome represents a promising avenue to elucidate their underlying pathophysiology. Using discriminatory statistical methods to disentangle disease signals from one another and potential confounders, we characterized microbial signatures shared and distinct among these diseases for the first time, and established the baseline microbiota of a mixed prospective cohort. We identified a shared immune-mediated disease signal, represented by lower abundances of Lachnospiraceae taxa, most notably Blautia and Ruminococcus gauvreauii group. Patients with SpA were specifically enriched in Collinsella and Lactobacillus co-occurring with increased inflammation, while HLA-B27+ individuals displayed enriched Faecalibacterium. Our results indicate that the shared depletion of short-chain fatty acid producing Lachnospiraceae taxa may stem from different dysbiotic states previously described as enterotypes, which reflect long-term dietary and medication patterns and capture persistent, idiosyncratic variation between individuals.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 90%

Spondyloarthritis, acute anterior uveitis, and Crohn’s disease have both shared and distinct gut microbiota

Essex

Rodriguez

Rademacher

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Despite the downregulation of tryptophan levels, the levels of its derivatives, which are involved in the kynurenine pathway, serotonin pathway and indole derivative pathway, were found to be elevated. Two independent studies observed upregulation of kynurenine levels in the serum of AS and JIA patients (Korte-Bouws et al, 2019;Eryavuz Onmaz et al, 2021). Eryavuz Onmaz et al (2021) observed increased quinolinic acid levels and decreased levels of kynurenic acid and 3-hydroxykynurenine, which were more different in newly diagnosed AS groups than in therapy groups when compared with healthy controls.…”

Section: Amino Acid Metabolismmentioning

confidence: 98%

“…7 studies analyzed the dynamic alterations in metabolic profiles in SpA patients before and after treatment (Gao et al, 2008;Kapoor et al, 2013;Nanus et al, 2015;Butbul et al, 2020;Bogunia-Kubik et al, 2021;Funk and Becker, 2021;Gupta et al, 2021;Ou et al, 2021). Regarding the metabolomic analysis in different subtypes of SpA, 13 studies included AS patients (Gao et al, 2008;Fischer et al, 2012;Jiang et al, 2013;Chen et al, 2015;Shao et al, 2016;Wang et al, 2016;He et al, 2019;Bogunia-Kubik et al, 2021;Eryavuz Onmaz et al, 2021;Lv et al, 2021;Onmaz et al, 2021;Ou et al, 2021). 7 studies included PsA patients (Madsen et al, 2010;Kapoor et al, 2013;Armstrong et al, 2014;Nanus et al, 2015;Souto-Carneiro et al, 2020;Bogunia-Kubik et al, 2021;Rocha et al, 2021).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Metabolomic analysis in spondyloarthritis: A systematic review

Huang

Pu²,

Wang³

et al. 2022

Front. Microbiol.

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Spondyloarthritis (SpA) is a group of rheumatic diseases that cause joint inflammation. Accumulating studies have focused on the metabolomic profiling of SpA in recent years. We conducted a systematic review to provide a collective summary of previous findings on metabolomic profiling associated with SpA. We systematically searched PubMed, Medline, Embase and Web of Science for studies on comparisons of the metabolomic analysis of SpA patients and non-SpA controls. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included articles. From 482 records identified, 31 studies were included in the analysis. A number of metabolites were differentially distributed between SpA and non-SpA cases. SpA patients showed higher levels of glucose, succinic acid, malic acid and lactate in carbohydrate metabolism, higher glycerol levels and lower fatty acid (especially unsaturated fatty acid) levels in lipid metabolism, and lower levels of tryptophan and glutamine in amino acid metabolism than healthy controls. Both conventional and biological therapy of SpA can insufficiently reverse the aberrant metabolism state toward that of the controls. However, the differences in the results of metabolic profiling between patients with SpA and other inflammatory diseases as well as among patients with several subtypes of SpA are inconsistent across studies. Studies on metabolomics have provided insights into etiological factors and biomarkers for SpA. Supplementation with the metabolites that exhibit decreased levels, such as short-chain fatty acids (SCFAs), has good treatment prospects for modulating immunity. Further studies are needed to elucidate the role of disordered metabolic molecules in the pathogenesis of SpA.

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“…[18] Inflammation has been shown to be correlated with an alteration in kynurenine pathway. [19] Hydroxykynurenine is produced from kynurenine metabolism. These negative effects of amino acid metabolism can be relieved by P30K treatment.…”

Section: P30k Intervention Alters the Global Serum Metabolic Profile ...mentioning

confidence: 99%

A Novel Ultrafiltrate Extract of Propolis Exerts Anti‐inflammatory Activity through Metabolic Rewiring

Wu,

Zhu,

Zhou

et al. 2024

Chemistry & Biodiversity

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Thousands of years ago humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti‐inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase‐2 (COX‐2) was 8.30 µg/mL. The anti‐inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)‐induced acute liver and lung injury. Mechanistically, integrated GC‐MS and LC‐MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro‐inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol‐O‐methyltransferases (COMT), 11β‐hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

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Altered kynurenine pathway metabolism in patients with ankylosing spondylitis

Cited by 19 publications

References 40 publications

Spondyloarthritis, acute anterior uveitis, and Crohn’s disease have both shared and distinct gut microbiota

Spondyloarthritis, acute anterior uveitis, and Crohn’s disease have both shared and distinct gut microbiota

Metabolomic analysis in spondyloarthritis: A systematic review

A Novel Ultrafiltrate Extract of Propolis Exerts Anti‐inflammatory Activity through Metabolic Rewiring

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