Host-microbiome interactions in cardiovascular disease

1 PhD project offered in the IPP winter call 2022

Scientific background

The gut microbiome is by far the densest and metabolically active human-associated microbial community and is essential for health. Alterations in the microbiota (i.e. dysbiosis) can not only impair important commensal functions (e.g. immune modulation, pathogen exclusion), but also trigger or maintain pathomechanisms. While sequence-based analysis (metagenomics) of the gut microbiome has linked shifts in its composition to a variety of diseases, it is still rarely studied as an integral component and dynamic actor in systems medicine. Recently, we have demonstrated one such example of dynamic interaction between the host, microbiome and drugs in co-morbidity development linked to obesity (Vieira-Silva et al., Nature, 2020). With increasing body mass the prevalence of gut dysbiosis increases, but most importantly, for the same obesity index, the level of inflammation is significantly higher when individuals host a dysbiotic intestinal microbiome. Furthermore, this adverse interaction between host and microbiome is significantly attenuated by intake of the lipid-lowering medication statins (Vieira-Silva et al., Nature, 2020).

PhD project: Host-microbiome interactions in cardiovascular disease

This project aims to investigate in more detail the interactions between the host, gut microbiome and medication in the context of atherosclerotic cardiovascular disease and atherothrombosis using a quantitative systems medicine approach. The project will take advantage of large prospective cohorts at UMC Mainz (Gutenberg Health Study (GHS), Prof. Dr P. Wild) which include comprehensive clinical phenotyping and biomaterial collection. Since the progression of cardiovascular disease has heterogeneous causes and manifestations, the project aims to obtain a deeper mechanistic understanding of the role of host-microbiome interactions during disease progression and divergent manifestations; the early prediction of disease development risk; and the stratification of patients for optimal care and drug allocation. The project will combine wetlab techniques for microbiome research with computational biology for omics and clinical data integration. We are looking for candidates interested in interdisciplinary research for which openness and flexibility are essential. Experience in omics data analysis is a plus.

Publications relevant for this project

Vieira-Silva S*, Falony G*, Belda E*, [MetaCardis Consortium], Clément K, Raes J. (2020) Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature (581), 310–315

Falony G, Vieira-Silva S & Raes J. (2018) Richness and ecosystem development across faecal snapshots of the gut microbiota.Nat. Microbiol. 3, 526–528

Falony G*, Joossens M*, Vieira-Silva S*, Wang J*, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D, Tito RY, Chaffron S, Rymenans L, Verspecht C, De Sutter L, Lima-Mendez G, D’hoe K, Jonckheere K, et al. (2016) Population-level analysis of gut microbiome variation. Science 352, 560–4

 

Contact

Dr Sara Vieira-Silva
Email