| 1. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 2. |
- Jurga, Juliane, et al.
(författare)
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Pretreatment With P2Y12 Inhibitors in Patients With Chronic Coronary Syndrome Undergoing Percutaneous Coronary Intervention : A Report From the Swedish Coronary Angiography and Angioplasty Registry
- 2021
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Ingår i: Circulation. Cardiovascular Interventions. - : NLM (Medline). - 1941-7640 .- 1941-7632. ; 14:11, s. 1086-1093
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with chronic coronary syndrome undergoing percutaneous coronary intervention, the optimal timing of P2Y12 inhibitors' administration is uncertain. We compared pretreatment versus treatment in the catheterization laboratory (In-Cathlab) in a real-world population.METHODS: In Swedish Coronary Angiography and Angioplasty Registry, all patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, between 2006 and 2017 were identified. Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography, outside the catheterization laboratory. Outcomes were net adverse clinical events including death, myocardial infarction, stroke, or bleeding within 30 days of the index procedure and in-hospital bleeding.RESULTS: We included 26 814 patients, 8237 in the In-Cathlab, and 18 577 in the pretreatment group. In-Cathlab treatment compared with pretreatment was associated with lower risk for net adverse clinical event (4.2 versus 5.1%, adjusted hazard ratio 0.79 [0.63-0.99]), bleeding (2.3 versus 2.6%, adjusted hazard ratio, 0.76 [0.57-1.01]). and in-hospital bleeding (1.9 versus 2.1%, adjusted odds ratio, 0.70 [0.51-0.96]). The risk for death, myocardial infarction, or stroke did not significantly differ between the groups. Among the In-Cathlab treated patients, 41% received ticagrelor or prasugrel and 59% clopidogrel. Treatment with ticagrelor or prasugrel was associated with higher risk for net adverse clinical events (5.4% versus 3.4%, adjusted hazard ratio, 1.66 [1.12-2.48]), bleeding (3.4 versus 1.6%, adjusted hazard ratio, 2.14 [1.34-3.42]), and in-hospital bleeding (2.9 versus 1.2%, adjusted odds ratio, 2.24 [1.29-3.90]) but similar risk for death, myocardial infarction, or stroke, compared with clopidogrel.CONCLUSIONS: In patients with chronic coronary syndrome undergoing coronary angiography and ad hoc percutaneous coronary intervention, pretreatment with P2Y12 inhibitors, before arrival to the catheterization laboratory, was not associated with improved clinical outcomes but was associated with increased risk for bleeding. Our data support clopidogrel administration in the catheterization laboratory as the standard of care. Graphic Abstract: A graphic abstract is available for this article.
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| 3. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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