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dc.contributor.authorZhang, Yan, Ph.D.
dc.contributor.authorBrady, Arthur, Ph.D.
dc.contributor.authorJones, Cheron
dc.identifier.citationZhang Y, Brady A, Jones C., et al. (2018) Compositional and functional differences in the human gut microbiome correlate with clinical outcome following infection with wild-type Salmonella enterica serovar Typhi. mBio, 9:e00686-18. DOI: .00686-18en_US
dc.descriptionAdditional authors: Song, Yang; Darton, Thomas C.; Jones, Claire; Blohmke, Christoph J.; Pollard, Andrew J.; Magder, Laurence S.; Fasano, Alessio; Sztein, Marcelo B.; Fraser, Claire M.en_US
dc.description.abstractInsights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut micro-biota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from either Methanobrevibacter or a diverse representation of genera in the Firmicutes phylum. Immunization with one of two live oral attenuated vaccines against S. Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-type S. Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge with S. Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-type S. Typhi.en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.subject.meshGastrointestinal Microbiome--immunologyen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshImmunity, Mucosalen_US
dc.subject.meshRNA, Ribosomal, 16Sen_US
dc.subject.meshTyphoid Feveren_US
dc.titleCompositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type Salmonella enterica Serovar Typhien_US
dc.description.urinameFull Texten_US

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