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Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe(-/-) Mice

Journal article
Authors Annika Lindskog Jonsson
Robert Caesar
Rozita Akrami
Christopher Reinhardt
Frida Fåk
Jan Borén
Fredrik Bäckhed
Published in Arteriosclerosis Thrombosis and Vascular Biology
Volume 38
Issue 10
Pages 2318-2326
ISSN 1079-5642
Publication year 2018
Published at Wallenberg Laboratory
Pages 2318-2326
Language en
Keywords animals, atherosclerosis, choline, gastrointestinal microbiome, mice, c-reactive protein, coronary-artery-disease, trimethylamine-n-oxide, statin therapy, bile-acids, metabolism, cholesterol, inflammation, mouse, phosphatidylcholine, Hematology, Cardiovascular System & Cardiology
Subject categories Clinical Medicine


Objective To investigate the effect of gut microbiota and diet on atherogenesis. Approach and Results Here, we investigated the interaction between the gut microbiota and diet on atherosclerosis by feeding germ-free or conventionally raised Apoe(-/-) mice chow or Western diet alone or supplemented with choline (which is metabolized by the gut microbiota and host enzymes to trimethylamine N-oxide) for 12 weeks. We observed smaller aortic lesions and lower plasma cholesterol levels in conventionally raised mice compared with germ-free mice on a chow diet; these differences were not observed in mice on a Western diet. Choline supplementation increased plasma trimethylamine N-oxide levels in conventionally raised mice but not in germ-free mice. However, this treatment did not affect the size of aortic lesions or plasma cholesterol levels. Gut microbiota composition was analyzed by sequencing of 16S rRNA genes. As expected, the global community structure and relative abundance of many taxa differed between mice fed chow or a Western diet. Choline supplementation had minor effects on the community structure although the relative abundance of some taxa belonging to Clostridiales was altered. Conclusions In conclusion, the impact of the gut microbiota on atherosclerosis is dietary dependent and is associated with plasma cholesterol levels. Furthermore, the microbiota was required for trimethylamine N-oxide production from dietary choline, but this process could not be linked to increased atherosclerosis in this model.

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