A sound microbiota in a sound body through apolipoprotein A-I and HDL: from mouse models to humans
|Partner Organization||Partner Country|
|Université Paris-Saclay (INRA)||France|
|Berlin Institute of Health (BIH)||Germany|
1. Overall project description
The main objectives and expected results of the OCTOPUS project are the following:
- to determine, in genetically modified mouse models, to what extent different levels of apoA-I/HDL modulate gut microbiota composition, intestinal homeostasis/immunity, plasma metabolome and atherosclerosis development.
- to determine whether apoA-I/HDL levels can modulate gut microbiota composition and plasma metabolome in human cohorts, and to identify possible correlations between microbiota composition and metabolic parameters.
- to conduct SNPs analyses to highlight polymorphisms in genes involved in the microbiota-host cross-talk which could influence apoA-I/HDL levels.
- to disseminate to the general public, scientific community, and stakeholders the scientific questions, aims, initiatives and results of the project.
Expected impacts. Extensive laboratory research in the past decade has helped to unravel some of the biological and genetic bases of atherosclerosis; in addition, improved treatments have reduced the number of deaths from atherosclerosis-related diseases in high-income countries. Despite this progress, atherosclerosis remains a common health problem. People dying from cardiovascular diseases will expand to reach 23.3 million by 2030 and over 80% of these deaths will take place in low- and middle-income countries. This project is aimed at investigating the so far unexplored cross-talk between dyslipidemia, apoA-I/HDL levels and gut microbiota in the pathophysiology of atherosclerosis. The expected findings will possibly help in unravelling new mechanisms involved in plaque development and in promoting the search for new therapeutic targets/approaches.
The results obtained will potentially open a completely new scenario and shed a light on an aspect of apoA-I/HDL biology never investigated before. The scientific benefits deriving from the project are fourfold and may yield novel insights for treating cardiovascular disease by: i) demonstrating whether apoA-I/HDL influences atherosclerosis development by modulating the presence of TMAO-producing (or other) bacteria in the gut; ii) clarifying how apoA-I/HDL modulates gut microbiota composition by regulating intestinal homeostasis and immunity/inflammation; iii) highlighting polymorphisms in genes involved in the microbiota-host cross-talk which could influence apoA-I/HDL levels; iv) identifying metabolic biomarkers of dysbiosis associated to cardiovascular disease.
These outcomes will potentially translate into benefits for stakeholders (companies/enterprises, physicians, patients). Specifically, the identification of novel beneficial bacterial species able to impact on atherosclerosis development will spur companies/enterprises to produce new prebiotic/probiotic formulations directed at the huge market of dyslipidemic/cardiovascular patients. These formulations will provide physicians with new tools, acting synergistically with existing personalized dietary approaches or pharmacological treatments. Similarly, the identification of endogenous or microbially-derived biomarkers will draw companies/enterprises to invest in the production of diagnostic kits potentially helping in the stratification and management of patients according to their cardiovascular risk.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Partners Number||Doi|
|Delgado GE*, Krämer BK, Scharnagl H, Fauler G, Stojakovic T, März W, Kleber ME*, Lammert A||Bile Acids in Patients with Uncontrolled Type 2 Diabetes Mellitus - The Effect of Two Days of Oatmeal Treatment.||10.1055/a-1069-7330.|
|Delgado GE*, Krämer BK, Siekmeier R, Yazdani B, März W, Leipe J, Kleber ME*||Influence of smoking and smoking cessation on biomarkers of endothelial function and their association with mortality.||10.1016/j.atherosclerosis.2019.11.017.|
|Busnelli M*, Manzini S*, Jablaoui A, Bruneau A, Kriaa A, Philippe C, Arnaboldi F, Colombo A, Ferrari B, Ambrogi F*, Maguin E, Rhimi M, Chiesa G*, Gérard P*||Fat-Shaped Microbiota Affects Lipid Metabolism, Liver Steatosis, and Intestinal Homeostasis in Mice Fed a Low-Protein Diet.||0.1002/mnfr.201900835|
|Yazdani B, Kleber ME*, Yücel G, Delgado GE*, Benck U, Krüger B, März W, Krämer BK.||Association of double product and pulse pressure with cardiovascular and all-cause mortality in the LURIC study.||10.1111/jch.14067|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|Scientists||Graciela Delgado*, Winfried März, Marcus E. Kleber*, Marco Busnelli*, Philippe Gérard*, Olivia Gräbner*, Giulia Chiesa*, A sound microbiota in a sound body through apolipoprotein A-I and HDL: from mouse models to humans (The OCTOPUS Consortium), Biomarkermeeting, Mannheim, 2019||Poster|
|General public||Marco Busnelli*, Giulia Chiesa*, Stefano Manzini*, HDL, aterosclerosi e… microrganismi intestinali: parte uno studio per studiarne lo stretto rapporto, University of Milan RicercaMix Blog, 2019||Blog post|
|Scientists, General Public||Marco Busnelli*, Giulia Chiesa*, Stefano Manzini*, A sound microbiota in a sound body through apolipoprotein A-I and HDL, Hot Nut 2: Hot Topics in Nutrition, Università degli Studi di Milano, Milan, 2019||Talk|
|General Public||Marco Busnelli*, Interview about Hot Nut 2 talk, by https://microbioma.it/, 2019||Talk / Interview|
|Scientists||Stefano Manzini*, Genetic HDL deficiency: insights from a double knock-out mouse model, Rare Disorders of Lipid Metabolism: from Phenotype to Precision Medicine, Università degli Studi di Milano, Milan, 2019||Talk|
|General public||Consortium, Upkeeping of Project Website. Migration of the site to a long-term domain, URL: https://piermatteobaramban.wixsite.com/octopus||Website|
|General public||Consortium, OCTOPUS Facebook social page. The page hosts multilingual (Italian and English) content related to the Project’s activities, with topics ranging from everyday lab work and routine, to the interesting news in the field. Further, Projects meetings and activities are advertised. Date of activity: 12/02/2019 – current Total posts: 88 Followers: 220 Coverage (mean ± SD): 311 ± 342 Clicks (mean ± SD): 42.0 ± 43.2 Highest coverage: 1,753 Highest clicks: 250||Social media|
|General public||Consortium, OCTOPUS Twitter social account. The account hosts multilingual (Italian and English) content related to the Project’s activities, with topics ranging from everyday lab work and routine, to the interesting news in the field. Further, Projects meetings and activities are advertised. Date of activity: 12/02/2019 – current Total tweets: 132 Followers: 20||Social media|
|Scientists||Marco Busnelli*, Stefano Manzini*, Maria Conti, Giulia Chiesa* Impact Of Dietary Choline On Atherosclerosis Development In Conventionally Raised Apoe-KO Mice Expressing Different Levels Of Apoa-I, 87th EAS Congress, Maastricht, 2019||Talk|
|Scientists||Graciela Delgado*, Marcus Kleber*, Influence of apoA-I levels on gene expression and DNA methylation in mice and humans: the OCTOPUS Consortium, Maikammer meeting, Klinischer Lipidstoffwechsel, Maikammer, 2019||Talk|
|General public||Coordinator, HDL e microbiota: un legame per curare l’aterosclerosi Journal: Platinum (Italian version), edited by PubliScoop Più, Il Sole 24 Ore. No. 070; Pub date: 22/03/2021||Press/Magazine|
|General public||Coordinator, HDL and microbiota: a possible link to treat atherosclerosis Journal: Platinum (English version), edited by PubliScoop Più, Il Sole 24 Ore. No. 070; Pub date: 22/03/2021||Press/Magazine|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|