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Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study.

Publication ,  Journal Article
Levade, I; Saber, MM; Midani, FS; Chowdhury, F; Khan, AI; Begum, YA; Ryan, ET; David, LA; Calderwood, SB; Harris, JB; LaRocque, RC; Qadri, F ...
Published in: J Infect Dis
February 3, 2021

BACKGROUND: Susceptibility to Vibrio cholerae infection is affected by blood group, age, and preexisting immunity, but these factors only partially explain who becomes infected. A recent study used 16S ribosomal RNA amplicon sequencing to quantify the composition of the gut microbiome and identify predictive biomarkers of infection with limited taxonomic resolution. 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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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

February 3, 2021

Volume

223

Issue

2

Start / End Page

342 / 351

Location

United States

Related Subject Headings

  • Vibrio cholerae
  • Severity of Illness Index
  • ROC Curve
  • Prognosis
  • Phylogeny
  • Microbiology
  • Metagenomics
  • Metagenome
  • Gastrointestinal Microbiome
  • Disease Susceptibility
 

Citation

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Levade, I., Saber, M. M., Midani, F. S., Chowdhury, F., Khan, A. I., Begum, Y. A., … Weil, A. A. (2021). Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study. J Infect Dis, 223(2), 342–351. https://doi.org/10.1093/infdis/jiaa358
Levade, Inès, Morteza M. Saber, Firas S. Midani, Fahima Chowdhury, Ashraful I. Khan, Yasmin A. Begum, Edward T. Ryan, et al. “Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study.J Infect Dis 223, no. 2 (February 3, 2021): 342–51. https://doi.org/10.1093/infdis/jiaa358.
Levade I, Saber MM, Midani FS, Chowdhury F, Khan AI, Begum YA, et al. Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study. J Infect Dis. 2021 Feb 3;223(2):342–51.
Levade, Inès, et al. “Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study.J Infect Dis, vol. 223, no. 2, Feb. 2021, pp. 342–51. Pubmed, doi:10.1093/infdis/jiaa358.
Levade I, Saber MM, Midani FS, Chowdhury F, Khan AI, Begum YA, Ryan ET, David LA, Calderwood SB, Harris JB, LaRocque RC, Qadri F, Shapiro BJ, Weil AA. Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study. J Infect Dis. 2021 Feb 3;223(2):342–351.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

February 3, 2021

Volume

223

Issue

2

Start / End Page

342 / 351

Location

United States

Related Subject Headings

  • Vibrio cholerae
  • Severity of Illness Index
  • ROC Curve
  • Prognosis
  • Phylogeny
  • Microbiology
  • Metagenomics
  • Metagenome
  • Gastrointestinal Microbiome
  • Disease Susceptibility