Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.

The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.

Abbreviated Duke Activity Status Index for Risk Stratification in Heart Failure.

The Duke activity status index (DASI), a self-administered 12-item questionnaire has been used to estimate functional capacity and recently demonstrated prognostic information. We aimed to develop an abbreviated version for clinical applications. Leveraging the Cleveland Clinic GeneBank Study, we developed an abbreviated DASI questionnaire (aDASI) with the machine learning XGBoost algorithm, with the goal of maintaining the accuracy and reliability of the original DASI.

Tumor cell-derived spermidine promotes a pro-tumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.

The glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine (SPD) is elevated in the GBM tumor microenvironment.

Kinetics of imidazole propionate from orally delivered histidine in mice and humans.

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation.