Project: A sound microbiota in a sound body through apolipoprotein A-I and HDL: from mouse models to humans

Acronym OCTOPUS (Reference Number: JTC-2017-3)
Project Topic What: ApoA-I/HDL has been recognized to exert a beneficial role in cholesterol homeostasis and immunity, and, as a consequence, to be anti-atherogenic. The OCTOPUS project aims to demonstrate, for the first time, that apoA-I/HDL can also modulate intestinal homeostasis and microbiota composition and notably, that an apoA-I/HDL deficiency-driven dysbiosis can predispose to atherosclerosis development. How: The OCTOPUS project originates from preliminary data elaborated by the Coordinator, and from published observations indicating that i) apoA-I deficient mice have an altered microbiota composition, enriched in choline-degrading bacteria; ii) gut microbiota can influence atherosclerosis development by metabolizing dietary choline. In this study it will be assessed to what extent different levels of apoA-I/HDL modulate gut microbiota composition, intestinal homeostasis/immunity, host metabolome and atherosclerosis development in atherosclerosis-prone, dyslipidemic mouse models and in two large human cohorts (PLIC, LURIC). In addition, microbiota from mice and humans with different levels of apoA-I/HDL will be transplanted in atherosclerosis-prone germ-free mice to mechanistically assess to what extent low apoA-I/HDL levels make the gut microbiota harmful for atherosclerosis development. The results obtained will potentially open a completely new scenario and shed light on an aspect of apoA-I/HDL biology that has not been investigated before. Who: The OCTOPUS consortium consists of four partners, coordinated by Giulia Chiesa, Università degli Studi di Milano (Italy); email contact: The other consortium partners are Marcus Kleber, University of Heidelberg and Olivia Gräbner, Metabolomic Discoveries GmbH (both Germany) and Philippe Gérard, INRA (France).
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Call HDHL-INTIMIC Cofunded Call "Interrelation of the Intestinal Microbiome, Diet and Health"

Project partner

Number Name Role Country
1 Università degli Studi di Milano Coordinator Italy
2 French National Institute for Agricultural Research (INRA), Toulouse Partner France
3 Heidelberg University Partner Germany
4 Metabolomic Discoveries GmbH Partner Germany