Abstract | BACKGROUND: METHODS: To achieve increased resolution of gut microbial factors associated with V. cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera. RESULTS: Using machine learning, we resolved species, strains, gene families, and cellular pathways in the microbiome at the time of exposure to V. cholerae to identify markers that predict infection and symptoms. Use of metagenomic features improved the precision and accuracy of prediction relative to 16S sequencing. We also predicted disease severity, although with greater uncertainty than our infection prediction. Species within the genera Prevotella and Bifidobacterium predicted protection from infection, and genes involved in iron metabolism were also correlated with protection. CONCLUSION: Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera.
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Authors | Inès Levade, Morteza M Saber, Firas S Midani, Fahima Chowdhury, Ashraful I Khan, Yasmin A Begum, Edward T Ryan, Lawrence A David, Stephen B Calderwood, Jason B Harris, Regina C LaRocque, Firdausi Qadri, B Jesse Shapiro, Ana A Weil |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 223
Issue 2
Pg. 342-351
(02 03 2021)
ISSN: 1537-6613 [Electronic] United States |
PMID | 32610345
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. |
Chemical References |
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Topics |
- Biomarkers
- Cholera
(diagnosis, microbiology)
- Disease Susceptibility
- Gastrointestinal Microbiome
- Metagenome
- Metagenomics
(methods)
- Phylogeny
- Prognosis
- ROC Curve
- Severity of Illness Index
- Vibrio cholerae
(physiology)
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