Eicosapentaenoic Acid-Enriched Phosphoethanolamine Plasmalogens Alleviated Atherosclerosis by Remodeling Gut Microbiota to Regulate Bile Acid Metabolism in LDLR^–/– Mice

Abstract

Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR–/–) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 α-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.

Plasmalogen Replacement Therapy

“…A similar result was obtained with PPI-1025 treatment, suggesting that the effect is independent of the acyl chain at the sn-2 position of the glycerol moiety and likely dependent on the vinyl-ether bond or on the entire plasmalogen molecule [98]. In hamster and mouse models of atherosclerosis, oral administration of PE-Pls decreased atherosclerosis lesion and total cholesterol and LDL cholesterol in serum [113,123]. In transgenic mice with small (due to depressed PI3K signaling) or failing hearts (due to dilated cardiomyopathy), OG treatment increased both PC-Pls and PE-Pls levels but did not impact heart size or function [114].…”

Soyasaponin A2 Alleviates Steatohepatitis Possibly through Regulating Bile Acids and Gut Microbiota in the Methionine and Choline‐Deficient (MCD) Diet‐induced Nonalcoholic Steatohepatitis (NASH) Mice

“…Diet or bioactive food component can modulate gut microbiota, which has been shown to contribute to the host health. [55] It is known that soyasaponins can be metabolized by the intestinal microbiota into soyasapogenol and thus may take part in the regulation of the intestinal microbiota. [27,40] However, no study is available regarding the effects of soyasaponins on the composition of gut microbiota.…”

Apostichopus japonicus Oligopeptide Induced Heterogeneity in the Gastrointestinal Tract Microbiota and Alleviated Hyperuricemia in a Microbiota‐Dependent Manner

“…Various results obtained over the past few decades imply that microbiota might be an important link between diets and host. [ 8–10 ] The microbiota is the entire set of microorganisms living in the gastrointestinal tract (GIT). Due to the difficulties involved in GIT sample collection, the microbiota in other segments of the GIT are poorly understood, except those in the rectum, which is represented by the fecal microbiota.…”