Prognostic value of plasma phenylalanine and gut microbiota-derived metabolite phenylacetylglutamine in coronary in-stent restenosis

Abstract

ObjectiveThis study was designed to explore the predictive value of plasma phenylalanine (Phe) and gut microbiota-derived metabolite phenylacetylglutamine (PAGln) in coronary in-stent restenosis (ISR).MethodsPatients with coronary ISR, in-stent hyperplasia (ISH), and in-stent patency (ISP) were retrospectively enrolled in this study. Multivariable logistic regression analyses were used to identify independent risk factors of ISR. The predictive value of plasma Phe and PAGln levels was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the ROC curve (AUCs) were compared using the Z-test. The correlation between PAGln and clinical characteristics were examined using Spearman's correlation analysis.ResultsSeventy-two patients (mean age, 64.74 ± 9.47 years) were divided into three groups according to coronary stent patency: ISR (n = 28), ISH (n = 11), and ISP (n = 33) groups. The plasma levels of Phe and PAGln were significantly higher in the ISR group than in the ISP group. PAGln was positively associated with the erythrocyte sedimentation rate, homocysteine, SYNTAX score, triglyceride to high-density lipoprotein ratio, Phe, and microbiota-related intermediate metabolite phenylacetic acid (PA). In the ISR group, with the aggravation of restenosis, PAGln levels were also elevated. In multivariate regression analyses, Phe, PAGln and SYNTAX score were independent predictors of coronary ISR (all P < 0.05). In the ROC curve analyses, both Phe [AUC = 0.732; 95% confidence interval (CI), 0.606–0.858; P = 0.002] and PAGln (AUC = 0.861; 95% CI, 0.766–0.957; P < 0.001) had good discrimination performance in predicting coronary ISR, and the predictive power of PAGln was significantly better (P = 0.031).ConclusionPlasma Phe and PAGln are valuable indices for predicting coronary ISR, and gut microbes may be a promising intervention target to prevent ISR progression.

Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling

“…In addition, the increased levels of phenylacetyl-L-glutamine 22 , 34 , 35 , 49 , 86 , a phenylalanine derivative, was identified in the blood and urine of PD patients in five studies. Phenylacetyl-L-glutamine was derived from phenylalanine through gut microbiota by decarboxylation and then conjugated with glutamine 87 , 88 . Therefore, the increased levels of phenylacetyl-L-glutamine are highly associated with the metabolism of phenylalanine and glutamine in PD, and reflect the high activity of gut microbiota in PD patients.…”

Investigating causal associations among gut microbiota, gut microbiota-derived metabolites, and gestational diabetes mellitus: a bidirectional Mendelian randomization study

“…PA is an organic compound primarily produced through microbial phenethylamine metabolism by bacteria [ 34 , 35 ]. Once absorbed into the portal system, PA can be converted by the liver into phenylacetylglutamine (PAGln) [ 36 ]. A cohort study involving 1,797 female twins demonstrated an association between PAGln and the expression of the cell death activator CIDE-C, which plays a role in regulating insulin resistance in adipose tissue [ 37 ].…”

Gut Microbiota and Cardiovascular Disease: Evidence on the Metabolic and Inflammatory Background of a Complex Relationship

“…PAGln has been associated with increased platelet activity and thrombosis potential [41]; recent studies point out that PAGln serum levels are correlated with coronary atherosclerosis severity and the incidence of CVD and MACE. Another study shows that high levels of PAGln are independently associated with an increased risk of coronary in-stent restenosis, which is a factor related to a worse prognosis in patients with CAD [42].…”