# Propionaat vermindert atherosclerose via immuunregulatie van intestinaal cholesterolmetabolisme

*geplaatst 2022-02-10 · Cholesterol · European heart journal · doi 10.1093/eurheartj/ehab644 · https://hartvaat.nl/2022/02/10/propionaat-vermindert-atherosclerose-via-immuunregulatie-van-intestinaal-cholest/*

Studie die aantoont dat propionaat (korte-keten vetzuur) atherosclerose vermindert via immuun-afhankelijke regulatie van intestinaal cholesterolmetabolisme.

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

This study demonstrated that propionate, a short-chain fatty acid produced by gut bacteria, attenuates atherosclerosis through immune-dependent regulation of intestinal cholesterol metabolism, advancing the microbiome-cardiovascular connection.

## Abstract (original, from the publication)

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. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels. CONCLUSION: Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.

Auteurs: Arash Haghikia, Friederike Zimmermann, Paul Schumann, Andrzej Jasina, Johann Roessler, David Schmidt, Philipp Heinze, Johannes Kaisler, Vanasa Nageswaran, Annette Aigner, Uta Ceglarek, Roodline Cineus, Ahmed N Hegazy, Emiel P C van der Vorst, Yvonne Döring, Christopher M Strauch, Ina Nemet, Valentina Tremaroli, Chinmay Dwibedi, Nicolle Kränkel, David M Leistner, Markus M Heimesaat, Stefan Bereswill, Geraldine Rauch, Ute Seeland, Oliver Soehnlein, Dominik N Müller, Ralf Gold, Fredrik Bäckhed, Stanley L Hazen, Aiden Haghikia, Ulf Landmesser

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Bron: European heart journal, https://doi.org/10.1093/eurheartj/ehab644. Bijgewerkt 2026-07-03T13:28:45Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.