The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context
Summary: Background: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423003572 |
| _version_ | 1797679402198237184 |
|---|---|
| author | Yulu Chen Kevin Mendez Sofina Begum Emily Dean Haley Chatelaine John Braisted Vrushali D. Fangal Margaret Cote Mengna Huang Su H. Chu Meryl Stav Qingwen Chen Nicole Prince Rachel Kelly Kenneth B. Christopher Joann Diray-Arce Ewy A. Mathé Jessica Lasky-Su |
| author_facet | Yulu Chen Kevin Mendez Sofina Begum Emily Dean Haley Chatelaine John Braisted Vrushali D. Fangal Margaret Cote Mengna Huang Su H. Chu Meryl Stav Qingwen Chen Nicole Prince Rachel Kelly Kenneth B. Christopher Joann Diray-Arce Ewy A. Mathé Jessica Lasky-Su |
| author_sort | Yulu Chen |
| collection | DOAJ |
| description | Summary: Background: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the existing physiologic state, unobserved via current clinical measures. Furthermore, metabolomics profiling during acute disease can be influenced by confounding factors such as indications, medical treatments, and lifestyles. Methods: We employed metabolomic profiling to cluster infection-free individuals and assessed their relationship with COVID severity and influenza incidence/recurrence. Findings: We identified a metabolomic susceptibility endotype that was strongly associated with both severe COVID (ORICUadmission = 6.7, p-value = 1.2 × 10−08, ORmortality = 4.7, p-value = 1.6 × 10−04) and influenza (ORincidence = 2.9; p-values = 2.2 × 10−4, βrecurrence = 1.03; p-value = 5.1 × 10−3). We observed similar severity associations when recapitulating this susceptibility endotype using metabolomics from individuals during and after acute COVID infection. We demonstrate the value of using metabolomic endotyping to identify a metabolically susceptible group for two–and potentially more–IDs that are driven by increases in specific amino acids, including microbial-related metabolites such as tryptophan, bile acids, histidine, polyamine, phenylalanine, and tyrosine metabolism, as well as carbohydrates involved in glycolysis. Interpretations: These metabolites may be identified prior to infection to enable protective measures for these individuals. Funding: The Longitudinal EMR and Omics COVID-19 Cohort (LEOCC) and metabolomic profiling were supported by the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health. |
| first_indexed | 2024-03-11T23:14:05Z |
| format | Article |
| id | doaj.art-01e21a40f57041d39c5e5ade3b00fa5c |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-11T23:14:05Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-01e21a40f57041d39c5e5ade3b00fa5c2023-09-21T04:37:13ZengElsevierEBioMedicine2352-39642023-10-0196104791The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in contextYulu Chen0Kevin Mendez1Sofina Begum2Emily Dean3Haley Chatelaine4John Braisted5Vrushali D. Fangal6Margaret Cote7Mengna Huang8Su H. Chu9Meryl Stav10Qingwen Chen11Nicole Prince12Rachel Kelly13Kenneth B. Christopher14Joann Diray-Arce15Ewy A. Mathé16Jessica Lasky-Su17Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USADivision of Preclinical Innovation, National Center for Advancing Translational Science, National Institutes of Health, Rockville, MD, USADivision of Preclinical Innovation, National Center for Advancing Translational Science, National Institutes of Health, Rockville, MD, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Renal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USAPrecision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston, MA, USADivision of Preclinical Innovation, National Center for Advancing Translational Science, National Institutes of Health, Rockville, MD, USA; Corresponding authors.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Corresponding author.Summary: Background: As new infectious diseases (ID) emerge and others continue to mutate, there remains an imminent threat, especially for vulnerable individuals. Yet no generalizable framework exists to identify the at-risk group prior to infection. Metabolomics has the advantage of capturing the existing physiologic state, unobserved via current clinical measures. Furthermore, metabolomics profiling during acute disease can be influenced by confounding factors such as indications, medical treatments, and lifestyles. Methods: We employed metabolomic profiling to cluster infection-free individuals and assessed their relationship with COVID severity and influenza incidence/recurrence. Findings: We identified a metabolomic susceptibility endotype that was strongly associated with both severe COVID (ORICUadmission = 6.7, p-value = 1.2 × 10−08, ORmortality = 4.7, p-value = 1.6 × 10−04) and influenza (ORincidence = 2.9; p-values = 2.2 × 10−4, βrecurrence = 1.03; p-value = 5.1 × 10−3). We observed similar severity associations when recapitulating this susceptibility endotype using metabolomics from individuals during and after acute COVID infection. We demonstrate the value of using metabolomic endotyping to identify a metabolically susceptible group for two–and potentially more–IDs that are driven by increases in specific amino acids, including microbial-related metabolites such as tryptophan, bile acids, histidine, polyamine, phenylalanine, and tyrosine metabolism, as well as carbohydrates involved in glycolysis. Interpretations: These metabolites may be identified prior to infection to enable protective measures for these individuals. Funding: The Longitudinal EMR and Omics COVID-19 Cohort (LEOCC) and metabolomic profiling were supported by the National Heart, Lung, and Blood Institute and the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health.http://www.sciencedirect.com/science/article/pii/S2352396423003572COVID-19 severityMetabolomicsMass general brigham biobankElectronic medical recordsEndotypesSimilarity network fusion |
| spellingShingle | Yulu Chen Kevin Mendez Sofina Begum Emily Dean Haley Chatelaine John Braisted Vrushali D. Fangal Margaret Cote Mengna Huang Su H. Chu Meryl Stav Qingwen Chen Nicole Prince Rachel Kelly Kenneth B. Christopher Joann Diray-Arce Ewy A. Mathé Jessica Lasky-Su The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context EBioMedicine COVID-19 severity Metabolomics Mass general brigham biobank Electronic medical records Endotypes Similarity network fusion |
| title | The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context |
| title_full | The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context |
| title_fullStr | The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context |
| title_full_unstemmed | The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context |
| title_short | The value of prospective metabolomic susceptibility endotypes: broad applicability for infectious diseasesResearch in context |
| title_sort | value of prospective metabolomic susceptibility endotypes broad applicability for infectious diseasesresearch in context |
| topic | COVID-19 severity Metabolomics Mass general brigham biobank Electronic medical records Endotypes Similarity network fusion |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423003572 |
| work_keys_str_mv | AT yuluchen thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT kevinmendez thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT sofinabegum thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT emilydean thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT haleychatelaine thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT johnbraisted thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT vrushalidfangal thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT margaretcote thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT mengnahuang thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT suhchu thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT merylstav thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT qingwenchen thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT nicoleprince thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT rachelkelly thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT kennethbchristopher thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT joanndirayarce thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT ewyamathe thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT jessicalaskysu thevalueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT yuluchen valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT kevinmendez valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT sofinabegum valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT emilydean valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT haleychatelaine valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT johnbraisted valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT vrushalidfangal valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT margaretcote valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT mengnahuang valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT suhchu valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT merylstav valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT qingwenchen valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT nicoleprince valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT rachelkelly valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT kennethbchristopher valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT joanndirayarce valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT ewyamathe valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext AT jessicalaskysu valueofprospectivemetabolomicsusceptibilityendotypesbroadapplicabilityforinfectiousdiseasesresearchincontext |