Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease
Abstract Crohn’s disease (CD) is characterised by chronic inflammation. We aimed to identify a relationship between plasma inflammatory metabolomic signature and genomic data in CD using blood plasma metabolic profiles. Proton NMR spectroscopy were achieved for 228 paediatric CD patients. Regression...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-18178-9 |
| _version_ | 1818497890205564928 |
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| author | Enrico Mossotto Joanna Boberska James J. Ashton Imogen S. Stafford Guo Cheng Jonathan Baker Florina Borca Hang T. T. Phan Tracy F. Coelho R. Mark Beattie Sandrine P. Claus Sarah Ennis |
| author_facet | Enrico Mossotto Joanna Boberska James J. Ashton Imogen S. Stafford Guo Cheng Jonathan Baker Florina Borca Hang T. T. Phan Tracy F. Coelho R. Mark Beattie Sandrine P. Claus Sarah Ennis |
| author_sort | Enrico Mossotto |
| collection | DOAJ |
| description | Abstract Crohn’s disease (CD) is characterised by chronic inflammation. We aimed to identify a relationship between plasma inflammatory metabolomic signature and genomic data in CD using blood plasma metabolic profiles. Proton NMR spectroscopy were achieved for 228 paediatric CD patients. Regression (OPLS) modelling and machine learning (ML) approaches were independently applied to establish the metabolic inflammatory signature, which was correlated against gene-level pathogenicity scores generated for all patients and functional enrichment was analysed. OPLS modelling of metabolomic spectra from unfasted patients revealed distinctive shifts in plasma metabolites corresponding to regions of the spectrum assigned to N-acetyl glycoprotein, glycerol and phenylalanine that were highly correlated (R2 = 0.62) with C-reactive protein levels. The same metabolomic signature was independently identified using ML to predict patient inflammation status. Correlation of the individual peaks comprising this metabolomic signature of inflammation with pathogenic burden across 15,854 unselected genes identified significant enrichment for genes functioning within ‘intrinsic component of membrane’ (p = 0.003) and ‘inflammatory bowel disease (IBD)’ (p = 0.003). The seven genes contributing IBD enrichment are critical regulators of pro-inflammatory signaling. Overall, a metabolomic signature of inflammation can be detected from blood plasma in CD. This signal is correlated with pathogenic mutation in pro-inflammatory immune response genes. |
| first_indexed | 2024-12-10T18:51:05Z |
| format | Article |
| id | doaj.art-99c44f320fda48c8b2bafae5f5d341cd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T18:51:05Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-99c44f320fda48c8b2bafae5f5d341cd2022-12-22T01:37:18ZengNature PortfolioScientific Reports2045-23222022-08-0112111110.1038/s41598-022-18178-9Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s diseaseEnrico Mossotto0Joanna Boberska1James J. Ashton2Imogen S. Stafford3Guo Cheng4Jonathan Baker5Florina Borca6Hang T. T. Phan7Tracy F. Coelho8R. Mark Beattie9Sandrine P. Claus10Sarah Ennis11Human Genetics and Genomic Medicine, Southampton General Hospital, University of SouthamptonDepartment of Food and Nutritional Sciences, The University of ReadingHuman Genetics and Genomic Medicine, Southampton General Hospital, University of SouthamptonHuman Genetics and Genomic Medicine, Southampton General Hospital, University of SouthamptonHuman Genetics and Genomic Medicine, Southampton General Hospital, University of SouthamptonDepartment of Paediatric Gastroenterology, Southampton Children’s HospitalNIHR Southampton Biomedical Research Centre, University Hospital SouthamptonNIHR Southampton Biomedical Research Centre, University Hospital SouthamptonDepartment of Paediatric Gastroenterology, Southampton Children’s HospitalDepartment of Paediatric Gastroenterology, Southampton Children’s HospitalDepartment of Food and Nutritional Sciences, The University of ReadingHuman Genetics and Genomic Medicine, Southampton General Hospital, University of SouthamptonAbstract Crohn’s disease (CD) is characterised by chronic inflammation. We aimed to identify a relationship between plasma inflammatory metabolomic signature and genomic data in CD using blood plasma metabolic profiles. Proton NMR spectroscopy were achieved for 228 paediatric CD patients. Regression (OPLS) modelling and machine learning (ML) approaches were independently applied to establish the metabolic inflammatory signature, which was correlated against gene-level pathogenicity scores generated for all patients and functional enrichment was analysed. OPLS modelling of metabolomic spectra from unfasted patients revealed distinctive shifts in plasma metabolites corresponding to regions of the spectrum assigned to N-acetyl glycoprotein, glycerol and phenylalanine that were highly correlated (R2 = 0.62) with C-reactive protein levels. The same metabolomic signature was independently identified using ML to predict patient inflammation status. Correlation of the individual peaks comprising this metabolomic signature of inflammation with pathogenic burden across 15,854 unselected genes identified significant enrichment for genes functioning within ‘intrinsic component of membrane’ (p = 0.003) and ‘inflammatory bowel disease (IBD)’ (p = 0.003). The seven genes contributing IBD enrichment are critical regulators of pro-inflammatory signaling. Overall, a metabolomic signature of inflammation can be detected from blood plasma in CD. This signal is correlated with pathogenic mutation in pro-inflammatory immune response genes.https://doi.org/10.1038/s41598-022-18178-9 |
| spellingShingle | Enrico Mossotto Joanna Boberska James J. Ashton Imogen S. Stafford Guo Cheng Jonathan Baker Florina Borca Hang T. T. Phan Tracy F. Coelho R. Mark Beattie Sandrine P. Claus Sarah Ennis Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease Scientific Reports |
| title | Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease |
| title_full | Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease |
| title_fullStr | Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease |
| title_full_unstemmed | Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease |
| title_short | Evidence of a genetically driven metabolomic signature in actively inflamed Crohn’s disease |
| title_sort | evidence of a genetically driven metabolomic signature in actively inflamed crohn s disease |
| url | https://doi.org/10.1038/s41598-022-18178-9 |
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