Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment
| العنوان: | Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment |
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| المؤلفون: | 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 |
| المصدر: | Molecular Metabolism Molecular Metabolism, Vol 36, Iss, Pp-(2020) Mol. Metab. 36:100976 (2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2212-8778 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9821ff0d08b8a5000e2c13b681378b1fTest http://europepmc.org/articles/PMC7183232Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9821ff0d08b8a5000e2c13b681378b1f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22128778 |
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