Associations of neopterin and kynurenine–tryptophan ratio with survival in primary sclerosing cholangitis

Dhillon, Amandeep Kaur; Rupp, Christian; Bergquist, Annika; Voitl, Robert; Folseraas, Trine; Trøseid, Marius; Midttun, Øivind; Ueland, Per Magne; Karlsen, Tom H.; Vesterhus, Mette; Kummen, Martin; Hov, Johannes Espolin Roksund

doi:10.1080/00365521.2021.1880627

Cited by 9 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…23,26,67,68 The ratio of tryptophan to kynurenine is predominantly mediated by indoleamine 2,3-dioxygenase activity and is generally associated with inflammation as well as immunomodulation in both infectious diseases and chronic inflammatory conditions, including neurological diseases such as Parkinson's disease, 69 diabetes, 70 and several autoimmune conditions such as rheumatoid arthritis, 71 systemic lupus erythematosus, 72 and primary sclerosing cholangitis. 73 Plasma taurine concentrations were also increased in the acute phase of COVID-19 23 but also appear substantially elevated in the 3 month follow-up patients with respect to controls (Figure 2C). Elevated taurine levels have previously been associated with liver injury and hepatotoxicity in man and experimental animals, 74 but high levels of taurine are also present in large quantities in cardiac and skeletal muscles 75,76 and muscle damage has been associated with taurinaemia as a measure of tissue damage.…”

Section: ■ Results and Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

et al. 2021

View full text Add to dashboard Cite

We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients ( n = 27) were compared with controls ( n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients ( n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine ( p = 3.6 × 10 –3 versus controls) and reduced glutamine/glutamate ratio ( p = 6.95 × 10 –8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower ( p = 4.2 × 10 –3 ) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ 2 p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a ...

show abstract

Section: ■ Results and Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Additionally, the translocation of Lactobacillus gasseri induced interleukin-17-mediated inflammatory injury in the liver of mice [106]. In humans, interferon γ-related biomarkers released from T cells were elevated in PSC and were correlated with transplant-free survival [107]. Abnormal high endotoxin accumulation has been shown in biliary epithelial cells of liver specimens of PSC (and also PBC) patients [108].…”

Section: Pscmentioning

confidence: 99%

The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl

Stadlbauer

2021

Nutrients

View full text Add to dashboard Cite

The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.

show abstract

“…However, specific changes in species involved in tryptophan metabolism were detected ( 90 ). Even though, research for new biomarkers in patients or animal models highlight the involvement of tryptophan and its metabolites in the pathogenesis of PSC ( 91 ) and NASH ( 92 ), the causal link with microbiota dysbiosis yet remains to be demonstrated.…”

Section: Gut-derived Metabolites and Molecular Pathwaysmentioning

confidence: 99%

Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases

et al. 2021

View full text Add to dashboard Cite

The gut-liver axis covers the bidirectional communication between the gut and the liver, and thus includes signals from liver-to-gut (e.g., bile acids, immunoglobulins) and from gut-to-liver (e.g., nutrients, microbiota-derived products, and recirculating bile acids). In a healthy individual, liver homeostasis is tightly controlled by the mostly tolerogenic liver resident macrophages, the Kupffer cells, capturing the gut-derived antigens from the blood circulation. However, disturbances of the gut-liver axis have been associated to the progression of varying chronic liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and primary sclerosing cholangitis. Notably, changes of the gut microbiome, or intestinal dysbiosis, combined with increased intestinal permeability, leads to the translocation of gut-derived bacteria or their metabolites into the portal vein. In the context of concomitant or subsequent liver inflammation, the liver is then infiltrated by responsive immune cells (e.g., monocytes, neutrophils, lymphoid, or dendritic cells), and microbiota-derived products may provoke or exacerbate innate immune responses, hence perpetuating liver inflammation and fibrosis, and potentiating the risks of developing cirrhosis. Similarly, food derived antigens, bile acids, danger-, and pathogen-associated molecular patterns are able to reshape the liver immune microenvironment. Immune cell intracellular signaling components, such as inflammasome activation, toll-like receptor or nucleotide-binding oligomerization domain-like receptors signaling, are potent targets of interest for the modulation of the immune response. This review describes the current understanding of the cellular landscape and molecular pathways involved in the gut-liver axis and implicated in chronic liver disease progression. We also provide an overview of innovative therapeutic approaches and current clinical trials aiming at targeting the gut-liver axis for the treatment of patients with chronic liver and/or intestinal diseases.

show abstract

Associations of neopterin and kynurenine–tryptophan ratio with survival in primary sclerosing cholangitis

Cited by 9 publications

References 32 publications

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

The Gut-Liver Axis in Cholestatic Liver Diseases

Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases

Contact Info

Product

Resources

About