Firas S Midani1,2,3, Ana A Weil4,5, Fahima Chowdhury6, Yasmin A Begum6, Ashraful I Khan6, Meti D Debela4, Heather K Durand3, Aspen T Reese3,7, Sai N Nimmagadda8, Justin D Silverman1,2,3,9, Crystal N Ellis4,10, Edward T Ryan4,5,11, Stephen B Calderwood4,5,12, Jason B Harris4,13, Firdausi Qadri6, Lawrence A David1,2,3,8, Regina C LaRocque4,5. 1. Program in Computational Biology and Bioinformatics, Duke University, Durham, North Carolina. 2. Center for Genomic and Computational Biology, Duke University, Durham, North Carolina. 3. Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina. 4. Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts. 5. Department of Medicine, Harvard Medical School, Boston, Massachusetts. 6. Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka. 7. Department of Biology, Duke University, Durham, North Carolina. 8. Department of Biomedical Engineering, Duke University, Durham, North Carolina. 9. Medical Scientist Training Program, Duke University, Durham, North Carolina. 10. Massachusetts College of Pharmacy and Health Sciences University, Boston. 11. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts. 12. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts. 13. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Abstract
Background: Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood. Methods: We prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. Results: We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. Conclusion: These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.
Background: Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood. Methods: We prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. Results: We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. Conclusion: These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.
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