Infection leaves a genetic and functional mark on the gut population of a commensal bacterium

Gastrointestinal infection changes microbiome composition and gene expression. In this study, we demon-strate that enteric infection also promotes rapid genetic adaptation in a gut commensal. Measurements of Bacteroides thetaiotaomicron population dynamics within gnotobiotic mice reveal that these populations are relatively stable in the absence of infection, and the introduction of the enteropathogen Citrobacter rodentium reproducibly promotes rapid selection for a single-nucleotide variant with increased fitness. This mutation promotes resistance to oxidative stress by altering the sequence of a protein, IctA, that is essential for fitness during infection. We identified commensals from multiple phyla that attenuate the selec-tion of this variant during infection. These species increase the levels of vitamin B6 in the gut lumen. Direct administration of this vitamin is sufficient to significantly reduce variant expansion in infected mice. Our work demonstrates that a self-limited enteric infection can leave a stable mark on resident commensal pop-ulations that increase fitness during infection.

Automated summary

Gastrointestinal infection can alter microbiome composition and gene expression. This study reveals that enteric infection also leads to rapid genetic adaptation in gut commensals. By studying Bacteroides thetaiotaomicron population dynamics in gnotobiotic mice, it was observed that the introduction of the enteropathogen Citrobacter rodentium promotes selection of a single-nucleotide variant with increased fitness. This variant mutation enhances resistance to oxidative stress by affecting the sequence of a fitness essential protein, IctA. Furthermore, it was found that certain commensal species can attenuate the selection of this variant during infection and this attenuation is associated with increased levels of vitamin B6 in the gut lumen. Direct administration of vitamin B6 significantly reduces variant expansion in infected mice, indicating its potential as a therapeutic target in enteric infections.