Gut microbiota derived indoles are altered and associate with immune activation in moderate and severe carotid stenosis.

BACKGROUND

An imbalance of gut microbiota, their metabolites as well as inflammatory mediators have been increasingly linked to both atherosclerosis and stroke. However, data on microbiota derived tryptophan and histidine metabolites in carotid atherosclerosis are scarce.

PURPOSE: We investigated serum microbiota derived indoles, imidazole propionate (ImP) and trimethylamine N-oxide (TMAO), representing three distinct gut bacterial-related metabolites, in patients with carotid atherosclerosis compared with healthy controls with normal findings on carotid ultrasound. We aimed to examine their relation to plaque characteristics, immune activation markers and traditional cardiovascular risk factors.

METHODS

Thirty patients scheduled for carotid endarterectomy and 18 control subjects were included in this cross-sectional study. Carotid arteries were investigated with ultrasound. Indoles, ImP and TMAO were analyzed by liquid chromatography-tandem mass spectrometry, and Lipopolysaccharide (LPS) by a Limulus Amebocyte Lysate chromogenic assay.

RESULTS

Compared to controls, patients exhibited lower levels of indole-3-propionic acid (IPA) (p=0.004) and indole-3-acetic acid (IAA) (p = 0.030). In patients, higher levels of indole metabolites were associated with lower C-reactive protein. ImP and TMAO did not differ between patients and controls.

CONCLUSION

Patients with carotid atherosclerosis exhibited reduced serum concentrations of IPA and IAA, thought to have anti-inflammatory effects, and increased inflammatory markers, possibly suggesting disruptions in the gut-vascular-immune axis.