Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment
| Autor: | Marta Ballanti, Omero Alessandro Paoluzi, Massimo Federici, Anna Artati, Nikolaus Marx, Jerzy Adamski, Claudia Goettsch, Geltrude Mingrone, Maria Mavilio, Robert Stoehr, Bart Staels, Rémy Burcelin, Rossella Menghini, Michael Heiser, Giovanni Monteleone, Lorenzo De Angelis, Ben Arpad Kappel |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Serum Apolipoprotein B Mice Knockout ApoE Antibiotics Settore MED/09 Atherosclerosis Gut Microbiota Dysbiosis Metabolic Diversity Cross-omics Gut flora Feces Mice 0302 clinical medicine RNA Ribosomal 16S Cecum 2. Zero hunger Gut microbiota Metabolic diversity biology Middle Aged 3. Good health Anti-Bacterial Agents Disease Progression Metabolome Original Article Female Metabolic Networks and Pathways lcsh:Internal medicine medicine.drug_class 030209 endocrinology & metabolism 03 medical and health sciences Metabolomics medicine Animals Humans lcsh:RC31-1245 Molecular Biology Aged Bacteria Lipid metabolism Settore MED/13 - ENDOCRINOLOGIA Cell Biology medicine.disease biology.organism_classification Gastrointestinal Microbiome Metabolic pathway 030104 developmental biology Immunology biology.protein |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 36, Iss, Pp-(2020) Mol. Metab. 36:100976 (2020) |
| ISSN: | 2212-8778 |
| Popis: | 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. Highlights • Antibiotics exacerbate atherosclerosis independently of diet. • Gut microbiota and metabolic alpha diversity are reduced by antibiotics. • Pathways connected to atherogenesis are tryptophan and lipid metabolism. • Metabolic changes are linked to reduced Clostridia and Bacteroidetes in the gut. |
| Databáze: | OpenAIRE |
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