The gut microbiome across the cardiovascular risk spectrum

Prins, F. M.; Collij, V.; Groot, H. E.; Björk, J. R.; Swarte, J. C.; Andreu-Sanchez, S.; Jansen, B. H.; Fu, J.; Harmsen, H. J. M.; Zhernakova, A.; Lipsic, E.; Van der Harst, P.; Weersma, R. K.; Gacesa, R.

doi:10.1101/2023.06.28.546971

bioRxiv · 10.1101/2023.06.28.546971

The gut microbiome across the cardiovascular risk spectrum

Prins, F. M.·Collij, V.·Groot, H. E.·Björk, J. R.·Swarte, J. C.·Andreu-Sanchez, S.·Jansen, B. H.·Fu, J.·Harmsen, H. J. M.·Zhernakova, A.·Lipsic, E.·Van der Harst, P.·Weersma, R. K.·Gacesa, R.

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Abstract

RationaleDespite significant progress in treatment strategies, cardiovascular disease remains a leading cause of death worldwide. Identifying new potential targets is crucial for enhancing preventive and therapeutic strategies. The gut microbiome has been associated with the development of coronary artery disease (CAD), however our understanding of the precise changes in the gut microbiome occurring during CAD development remains limited. ObjectiveTo investigate microbiome changes in participants without clinically manifest CAD with different cardiovascular risk levels and in patients with ST-elevation myocardial infarction (STEMI). Methods and ResultsIn this cross-sectional study we characterized the gut microbiome using metagenomics of 411 fecal samples from individuals with low (n=130), intermediate (n=130) and high (n=125) cardiovascular risk based on the Framingham score, and STEMI patients (n=26). We analyzed alpha and beta diversity of the gut microbiome and differential abundance of species and functional pathways among the different groups while accounting for confounders including medication and technical covariates. Abundances of Collinsella stercoris, Flavonifractor plautii and Ruthenibacterium lactatiformans showed a positive trend with cardiovascular risk, while Streptococcus thermophilus was negatively associated. Furthermore, in the differential abundance analysis we identified eight species and 49 predicted metabolic pathways that were differently abundant among the groups. These species included species linked to inflammation. Starch biosynthesis and phenolic compound degradation pathways were enriched in the gut microbiome of STEMI patients, while pathways associated with vitamin, lipid and amino-acid biosynthesis were depleted. ConclusionsWe identified four microbial species that demonstrated a gradual trend in their abundance from low risk individuals to those with STEMI, and species and pathways that were differently abundant in STEMI patients compared to groups without clinically manifest CAD. Further investigation is warranted to gain deeper understanding of their precise role in CAD progression and potential implications, with the ultimate goal of identifying novel therapeutic targets. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=142 HEIGHT=200 SRC="FIGDIR/small/546971v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@f7f0b1org.highwire.dtl.DTLVardef@1db0c8eorg.highwire.dtl.DTLVardef@154adeorg.highwire.dtl.DTLVardef@1e64c74_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender.com

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Prins, F. M., Collij, V., Groot, H. E., Björk, J. R., Swarte, J. C., Andreu-Sanchez, S., Jansen, B. H., Fu, J., Harmsen, H. J. M., Zhernakova, A., Lipsic, E., Van der Harst, P., Weersma, R. K., Gacesa, R.. 2023-07-03. The gut microbiome across the cardiovascular risk spectrum. https://doi.org/10.1101/2023.06.28.546971

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