Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection

Midani, Firas S; Weil, Ana A.; Chowdhury, Fahima; Begum, Yasmin; Khan, Ashraful Islam; Debela, Meti D.; Durand, Heather K.; Reese, Aspen T.; Nimmagadda, Sai N; Silverman, Justin D.; Ellis, Crystal N.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; Qadri, Firdausi; David, Lawrence A.; LaRocque, Regina C.

doi:10.1093/infdis/jiy192

Cited by 64 publications

(93 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We performed metagenomic sequencing of the gut microbiome in 65 contacts of cholera cases from a cohort described by Midani et al . (15), from which sufficient DNA remained for shotgun metagenomic sequencing. Of these 65 contacts, referred to as the Midani 2018 cohort, 20 developed infection during the follow-up period, and 45 remained uninfected ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…To put the metagenomic predictions in context, we next compared their predictive power and accuracy to clinical and demographic factors ( Table S1 ). Three of these factors (age, baseline vibriocidal antibodies and blood group) are known to impact susceptibility to V. cholerae infection (6,15) ( Table S5 ). The likelihood of developing infection was not predicted well using a RF model trained on the 7 features clinical and demographic factors (AUC=0.60, not significantly different from shuffled labels, p =0.66; Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…After presentation of a V. cholerae culture-positive index case to the hospital on day 1, household contacts were enrolled on day 2. The expanded cohort includes the Midani 2018 cohort (15), with an addition of 33 samples from infected individuals (13 asymptomatic and 2 symptomatic).…”

Section: Methodsmentioning

confidence: 99%

“…Studies of V. cholerae and the gut microbiota often focus on a limited number of bacterial species or involve patients who already have symptomatic cholera (8,14). One study to date has characterized the gut microbiome of individuals exposed to V. cholerae to predict susceptibility to infection (15). In this study, Midani et al .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

PredictingVibrio choleraeinfection and disease severity using metagenomics in a prospective cohort study

Levade

Saber

Midani

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

23 2 CORRESPONDING AUTHOR : jesse.shapiro@umontreal.ca 24 25 RUNNING TITLE: Stool metagenomics predicts cholera 26 ABSTRACT (word count: 196) 27 28Background: Susceptibility to Vibrio cholerae infection is impacted by blood group, age, and 29 pre-existing immunity, but these factors only partially explain who becomes infected. A recent 30 study used 16S rRNA amplicon sequencing to quantify the composition of the gut microbiome 31 and identify predictive biomarkers of infection with limited taxonomic resolution. 32 Methods:To achieve increased resolution of gut microbial factors associated with V. cholerae 33 susceptibility and identify predictors of symptomatic disease, we applied deep shotgun 34 metagenomic sequencing to a cohort of household contacts of patients with cholera. 35Results: Using machine learning, we resolved species, strains, gene families, and cellular 36 pathways in the microbiome at the time of exposure to V. cholerae to identify markers that 37 predict infection and symptoms. Use of metagenomic features improved the precision and 38 accuracy of prediction relative to 16S sequencing. We also predicted disease severity, although 39 with greater uncertainty than our infection prediction. Species within the genera Prevotella and 40Bifidobacterium predicted protection from infection, and genes involved in iron metabolism also 41 correlated with protection. 42 Conclusion:Our results highlight the power of metagenomics to predict disease outcomes and 43 suggest specific species and genes for experimental testing to investigate mechanisms of 44 microbiome-related protection from cholera. 45 46

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PredictingVibrio choleraeinfection and disease severity using metagenomics in a prospective cohort study

Levade

Saber

Midani

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a recent prospective household survey in Bangladesh, the authors found that abnormal gut microbial communities are host factors for susceptibility to V. cholerae infection. Susceptibility to cholera was associated with a decreased level of Bacteroides [64]. A study involving time-series metagenomic analysis of fecal samples collected during the acute diarrhea and recovery phases of cholera in a cohort of Bangladeshi adults found that recovery was characterized by a pattern of accumulation of bacterial taxa that showed similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children [65].…”

Section: Micro-organic Basis Of Pi-ibsmentioning

confidence: 99%

Post-infection irritable bowel syndrome in the tropical and subtropical regions: Vibrio cholerae is a new cause of this well-known condition

Ghoshal

Rahman²

2019

Indian J Gastroenterol

View full text Add to dashboard Cite

Can Non‐ToxigenicVibrio choleraeReduce a Cholera Infection?

Sela

Hammer

Halpern

2023

Israel Journal of Chemistry

View full text Add to dashboard Cite

Vibrio cholerae, is the causative agent of cholera, that infects millions, annually. Chironomids are aquatic insects that host V. cholerae. Toxigenic strains produce cholera toxin (CT) which is the main virulence factor that causes cholera symptoms. In contrast to other bacterial pathogens, V. cholerae produces CT when at low cell densities while hemagglutinin/protease (HAP) is a high cell density‐controlled gene. When V. cholerae behavior was examined on chironomids, we showed that high cell densities of non‐toxigenic strains, increased HAP production in a toxigenic strain, conditions which could also potentially reduce CT production. Here we propose the value of studies that could support the potential of V. cholerae non‐toxigenic strains to repress virulence gene expression in cholera‐infected humans. High cell densities of a non‐toxigenic strain present in an infected individual, may down‐regulate CT expression, reducing cholera symptoms. To further test the hypothesis supported by a chironomid model, additional experiments in animal models are first needed.

show abstract

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection

Abstract: These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

Cited by 64 publications

References 36 publications

PredictingVibrio choleraeinfection and disease severity using metagenomics in a prospective cohort study

PredictingVibrio choleraeinfection and disease severity using metagenomics in a prospective cohort study

Post-infection irritable bowel syndrome in the tropical and subtropical regions: Vibrio cholerae is a new cause of this well-known condition

Can Non‐ToxigenicVibrio choleraeReduce a Cholera Infection?

Contact Info

Product

Resources

About