Microbiota-Mediated Crosstalk Between the Gut and the Vascular System: Protective Effects of Novel Postbiotic Formulations on Human Endothelial and Vascular Smooth Muscle Cells

TL;DR

This study explores how gut microbiota metabolites protect vascular cells from oxidative and inflammatory damage, identifying specific probiotic formulations and their active components.

Contribution

The study identifies novel postbiotic formulations and their protective effects on vascular cells via the gut-vascular axis, with a focus on Limosilactobacillus reuteri-PBS072.

Findings

MIX-1 and MIX-3 showed the greatest protective effects against oxidative and inflammatory stress in vascular cells.

Limosilactobacillus reuteri-PBS072 was identified as a key contributor to the antioxidant effects of MIX-1 and MIX-3.

Probiotic supernatants partially utilized the SIRT1-pathway to exert antioxidant effects.

Abstract

The close connections between the intestine and distal systems, known as axes, are a growing focus of scientific research; however, the gut–vascular axis, particularly as a target of microbial metabolites, remains underexplored. In this study, three supernatants derived from probiotic formulations composed of Lactobacillus and Bifidobacterium strains (MIX-1, MIX-2, and MIX-3) were evaluated in counteracting vascular alterations associated with dysbiosis. Human aortic smooth muscle (HASMCs) and endothelial (HAECs) cells were exposed to pro-oxidative (H2O2) and pro-inflammatory (TMAO) stimuli. Concentrations up to 5–10% (v/v) were tolerated in both cell lines, with MIX-1 and MIX-3 showing the greatest protective efficacy. These formulations exerted antioxidant effects by reducing H2O2-induced ROS production and cell viability loss, and anti-inflammatory effects by limiting TMAO-induced IL-1β release. MIX-1 also attenuated TMAO-induced IL-6 release. Further analyses indicated a partial involvement of the SIRT1-pathway in its vascular antioxidant effects. Chromatographic profiling revealed comparable qualitative metabolites among the probiotic supernatants, while quantitative differences were observed, with higher lactate levels in MIX-1 and MIX-3 compared to MIX-2. Finally, we have determined that Limosilactobacillus reuteri-PBS072 is mainly responsible for the antioxidant effect of MIX-1 and MIX-3. Overall, these findings highlight the potential of probiotic-derived metabolites in modulating the gut–vascular axis and promoting vascular protection.

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