Gut microbiota-related modulation of immune mechanisms in post-infarction remodelling and heart failure.

The immune system has long been recognized as a key driver in the progression of heart failure (HF). However, clinical trials targeting immune effectors have consistently failed to improve patient outcome across different HF aetiologies. The activation of the immune system in HF is complex, involving a broad network of pro-inflammatory and immune-modulating components, which complicates the identification of specific immune pathways suitable for therapeutic targeting.

Modulation of the Serum Metabolome by the Short-Chain Fatty Acid Propionate: Potential Implications for Its Cholesterol-Lowering Effect.

(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism.

Modulatory role of gut microbiota in cholesterol and glucose metabolism: Potential implications for atherosclerotic cardiovascular disease.

Accumulating evidence suggests an important role of gut microbiota in physiological processes of host metabolism as well as cardiometabolic disease. Recent advances in metagenomic and metabolomic research have led to discoveries of novel pathways in which intestinal microbial metabolism of dietary nutrients is linked to metabolic profiles and cardiovascular disease risk. A number of metaorganismal circuits have been identified by microbiota transplantation studies and experimental models using germ-free rodents.

Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.

Aims: Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism.

Methods And Results: Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels.

Impact of the Gut Microbiota on Atorvastatin Mediated Effects on Blood Lipids.

Background And Aims: The mechanisms of interindividual variation of lipid regulation by statins, such as the low-density lipoprotein cholesterol (LDL) lowering effects, are not fully understood yet. Here, we used a gut microbiota depleted mouse model to investigate the relation between the gut microbiota and the regulatory property of atorvastatin on blood lipids.

Methods: Mice (C57BL/6) with intact gut microbiota or antibiotic induced abiotic mice (ABS) were put on standard chow diet (SCD) or high fat diet (HFD) for six weeks.