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Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model

Journal article
Authors K. Kasahara
K. A. Krautkramer
E. Org
K. A. Romano
R. L. Kerby
E. I. Vivas
M. Mehrabian
J. M. Denu
Fredrik Bäckhed
A. J. Lusis
F. E. Rey
Published in Nature Microbiology
Volume 3
Issue 12
Pages 1461-1471
ISSN 2058-5276
Publication year 2018
Published at Wallenberg Laboratory
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 1461-1471
Language en
Links dx.doi.org/10.1038/s41564-018-0272-...
Subject categories Microbiology in the medical area

Abstract

Humans with metabolic and inflammatory diseases frequently harbour lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we show that a prominent gut-associated butyrate-producing bacterial genus (Roseburia) is inversely correlated with atherosclerotic lesion development in a genetically diverse mouse population. We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to: impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization; lower systemic inflammation; and ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate reduces endotoxaemia and atherosclerosis development. Together, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis. © 2018, The Author(s), under exclusive licence to Springer Nature Limited.

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