1. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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2. |
- Cosyn, Jan, et al.
(författare)
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Disparity in embrasure fill and papilla height between tooth- and implant-borne fixed restorations in the anterior maxilla : a cross-sectional study
- 2013
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Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 40:7, s. 728-733
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The objective of the present study was to compare inter-proximal fill and papilla height between different embrasures. Material & Methods One hundred and fifty non-smoking consecutive patients (mean age 54, range 32–73; 63 males and 87 females) without periodontal disease were selected in a multidisciplinary practice during regular supportive care. All had been treated for multiple tooth loss in the anterior maxilla at least 1 year earlier by means of a fixed restoration on teeth (n = 50) or implants (n = 100) using straightforward procedures (without hard and/or soft tissue augmentation). Embrasure fill was assessed by means of Jemt's papilla index and papilla height was registered following local anaesthesia by means of bone sounding by one clinician. Results Tooth-pontic and tooth-implant embrasures demonstrated comparable inter-proximal fill and papilla height (≥58% Jemt's score 3; mean papilla height ≥4.1 mm). Between missing teeth, embrasure fill and papilla height were lower regardless of the embrasure type. The implant-implant and implant-pontic embrasure demonstrated comparable outcome (≤42% Jemt's score 3; mean papilla height ≤ 3.3 mm; p ≥ 0.416), which was significantly poorer when compared to the pontic-pontic embrasure (82% Jemt's score 3; mean papilla height 3.7 mm; p ≤ 0.019). Overall, papilla index and papilla height demonstrated a weak correlation (Spearman's correlation coefficient: 0.198; p = 0.002). Conclusions The re-establishment of a papilla is difficult when there is no tooth involved. In that scenario a short papilla should be expected and implant-borne restorations demonstrate the poorest outcome. Moreover, an implant with a pontic may not perform better than adjacent implants.
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3. |
- 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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4. |
- 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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