• Alexander Kurilshikov, Inge C L van den Munckhof, Lianmin Chen, Marc J Bonder, Kiki Schraa, Rutten Joost H W JHW Department of Internal Medicine and Radboud Center for Infectious Diseases (I.C.L.v.d.M., K.S., J.H.W.R., N.P.R., J.d.G., M.O., L.A.B.J., T.B., M.G.N, Niels P Riksen, Jacqueline de Graaf, Marije Oosting, Serena Sanna, Joosten Leo A B LAB Department of Internal Medicine and Radboud Center for Infectious Diseases (I.C.L.v.d.M., K.S., J.H.W.R., N.P.R., J.d.G., M.O., L.A.B.J., T.B., M.G.N., Marinette van der Graaf, Tessa Brand, Debby P Y Koonen, Martijn van Faassen, LifeLines DEEP Cohort Study, BBMRI Metabolomics Consortium, P Eline Slagboom, Ramnik J Xavier, Folkert Kuipers, Marten H Hofker, Cisca Wijmenga, Mihai G Netea, Alexandra Zhernakova, and Jingyuan Fu.
• From the Department of Genetics (A.K., L.C., M.J.B., S.S., C.W., A.Z., J.F.), University of Groningen, University Medical Center Groningen, the Netherlands.
• Circ. Res. 2019 Jun 7; 124 (12): 1808-1820.

RationaleAltered gut microbial composition has been linked to cardiovascular diseases (CVDs), but its functional links to host metabolism and immunity in relation to CVD development remain unclear.ObjectivesTo systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes, and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts.Methods And ResultsWe assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based LLD (Lifelines DEEP) cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, sex, and body mass index, the gut microbiome could explain ≤11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL, and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a Ruminococcus species were associated to cardiovascular phenotypes in obese individuals, namely atherosclerosis and liver fat content, respectively. Integration of microbiome-diet-inflammation analysis in relation to metabolic risk score of CVD in the population cohort revealed 48 microbial pathways associated to CVD risk that were largely independent of diet and inflammation. Our data also showed that plasma levels rather than fecal levels of short-chain fatty acids were relevant to inflammation and CVD risk.ConclusionsThis study presents the largest metagenome-based association study on plasma metabolism and microbiome relevance to diet, inflammation, CVD risk, and cardiometabolic phenotypes in both population-based and clinical obesity cohorts. Our findings identified novel bacterial species and pathways that associated to specific lipoprotein subclasses and revealed functional links between the gut microbiome and host health that provide a basis for developing microbiome-targeted therapy for disease prevention and treatment.

29 keywords...

hide…