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- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
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| 3. |
- Gredal, H., et al.
(författare)
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Diagnosis and long-term outcome in dogs with acute onset intracranial signs
- 2020
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Ingår i: Journal of Small Animal Practice. - : Wiley. - 0022-4510 .- 1748-5827. ; 61:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate dogs with acute onset of intracranial signs suspected of stroke by primary veterinary clinicians, and establish possible differential diagnoses and long-term outcome. In addition, serum C-reactive protein and plasma cytokines were investigated as potential biomarkers of disease. Materials and Methods: All cases were evaluated by neurologic examination, routine haematology and biochemistry and measurement of serum C-reactive protein, plasma cytokine concentrations (interleukin-2, -6, -8, -10, tumour necrosis factor) and low-field MRI. Results: Primary veterinarians contacted the investigators with 85 suspected stroke cases. Only 20 met the inclusion criteria. Of these, two were diagnosed with ischaemic stroke. Other causes were idiopathic vestibular syndrome (n=6), brain tumour (n=5) and inflammatory brain disease (n=2); in five cases a precise diagnosis could not be determined. Median survival times were: brain tumour, 3 days, idiopathic vestibular syndrome, 315 days, ischaemic stroke, 365 days and inflammatory central nervous system (CNS) disease, 468 days. The median plasma concentrations of interleukin-2, -6, -8, -10 or tumour necrosis factor were not significantly increased in any of the diagnosis groups compared to healthy controls. Serum C-reactive protein was higher in dogs with brain tumours and inflammatory brain disease but not above the upper bound of the reference interval. Clinical Significance: Dogs that present with acute onset intracranial disease may have ischaemic stroke but are more likely to have other causes. Many dogs with such acute onset of neurological dysfunction (brain tumours excluded) may recover within a couple of weeks despite their initial severe clinical appearance.
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