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

HDHL INTIMIC cofunded call “Interrelation of the Intestinal Microbiome, Diet and Health” (IM 2017)
A sound microbiota in a sound body through apolipoprotein A-I and HDL: from mouse models to humans
OCTOPUS
2018-07-01
2022-05-31
CHIESA Giulia
Università Degli Studi Milano
Italy

Consortium

Partner Organization Partner Country
Université Paris-Saclay (INRA)France
Heidelberg UniversityGermany
Berlin Institute of Health (BIH)Germany

1. Overall project description


1.1 Summary

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.


1.2 Highlights

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. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPDoiPdf
Marcus Kleber, Graciela Delgado (Partner 2)Bile Acids in Patients with Uncontrolled Type 2 Diabetes Mellitus - The Effect of Two Days of Oatmeal Treatment.2020, in press 10.1055/a-1069-7330.
Marcus Kleber, Graciela Delgado (Partner 2)Influence of smoking and smoking cessation on biomarkers of endothelial function and their association with mortality.2020, 292, 52-5910.1016/j.atherosclerosis.2019.11.017.

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
ScientistsGraciela 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, 2019Poster
General publicMarco Busnelli, Giulia Chiesa, Stefano Manzini, HDL, aterosclerosi e… microrganismi intestinali: parte uno studio per studiarne lo stretto rapporto, University of Milan RicercaMix Blog, 2019Blog post
Scientists, General PublicMarco 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, 2019TalkLink
General PublicMarco Busnelli, Interview about Hot Nut 2 talk, by https://microbioma.it/, 2019Talk / InterviewLink
ScientistsStefano 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, 2019Talk
General publicPublication and upkeeping of Project Website. URL: https://www.octopus-athero.org/WebsiteLink
General publicOCTOPUS 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: 55 Followers: 191 Coverage (mean ± SD): 353.1 ± 363.7 Clicks (mean ± SD): 51.7 ± 52.1 Highest coverage: 1,493 Highest clicks: 203Social mediaLink
General publicOCTOPUS 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: 77 Followers: 19Social mediaLink
ScientistsMarco 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, 2019Talk Link
ScientistsGraciela 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, 2019Talk

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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