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Kappel, B.A.* ; De Angelis, L.* ; Heiser, M.* ; Ballanti, M.* ; Stoehr, R.* ; Goettsch, C.* ; Mavilio, M.* ; Artati, A. ; Paoluzi, O.A.* ; Adamski, J. ; Mingrone, G.* ; Staels, B.* ; Burcelin, R.* ; Monteleone, G.* ; Menghini, R.* ; Marx, N.* ; Federici, M.*

Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment.

Mol. Metab. 36:100976 (2020)

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Objective: The metabolic influence of gut microbiota plays a pivotal role in the pathogenesis of cardiometabolic diseases. Antibiotics affect intestinal bacterial diversity, and long-term usage has been identified as an independent risk factor for atherosclerosis-driven events. The aim of this study was to explore the interaction between gut dysbiosis by antibiotics and metabolic pathways with the impact on atherosclerosis development.Methods: We combined oral antibiotics with different diets in an Apolipoprotein E-knockout mouse model linking gut microbiota to atherosclerotic lesion development via an integrative cross-omics approach including serum metabolomics and cecal 16S rRNA targeted metagenomic sequencing. We further investigated patients with carotid atherosclerosis compared to control subjects with comparable cardiovascular risk.Results: Here, we show that increased atherosclerosis by antibiotics was connected to a loss of intestinal diversity and alterations of microbial metabolic functional capacity with a major impact on the host serum metabolome. Pathways that were modulated by antibiotics and connected to atherosclerosis included diminished tryptophan and disturbed lipid metabolism. These pathways were related to the reduction of certain members of Bacteroidetes and Clostridia by antibiotics in the gut. Patients with atherosclerosis presented a similar metabolic signature as those induced by antibiotics in our mouse model.Conclusion: Taken together, this work provides insights into the complex interaction between intestinal microbiota and host metabolism. Our data highlight that detrimental effects of antibiotics on the gut flora are connected to a pro-atherogenic metabolic phenotype beyond classical risk factors.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Atherosclerosis ; Antibiotics ; Gut Microbiota ; Dysbiosis ; Metabolic Diversity ; Cross-omics; Aryl-hydrocarbon Receptor; Trimethylamine-n-oxide; Intima-media Thickness; Intestinal Microbiota; Sequence Data; Disease Risk; Inflammation; Activation; Plaque; Mice

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 36, Article Number: 100976

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Molekulare Endokrinologie und Metabolismus (MEM)

Grants Ministry of University (MIUR) Progetti di Ricerca di Interesse Nazionale (PRIN)
Fondazione Roma call for Non-Communicable Diseases NCD 2014, EU-FP7 EURHYTHDIA
Deutsche Herzstiftung (DHS)
Deutsche Stiftung fur Herzforschung (DSHF)
RWTH Aachen University (START)
University of Rome Tor Vergata
German Research Foundation (DFG)
EU-FP7 FLORINASH