Summary
Reversible genomic DNA-inversions control expression of numerous bacterial molecules in the human gut, but how this relates to disease remains uncertain. By analyzing metagenomic samples from six human Inflammatory Bowel Disease (IBD) cohorts combined with mice experimentation, we identified multiple invertible regions in which a particular orientation was correlated with disease. These include the promoter of the anti-inflammatory polysaccharide-A (PSA) of Bacteroides fragilis, which is mostly oriented ‘OFF’ during inflammation but switches to the ‘ON’ orientation when inflammation is resolved. We further detected increased abundances of B. fragilis associated bacteriophages in patients with the PSA ‘OFF’ orientation. Isolation and analysis of a B. fragilis associated bacteriophage revealed that it induced the PSA ‘OFF’ switch, thereby altering the bacterial induced immune modulation. Altogether, we reveal large-scale dynamic and reversible bacterial phase variations driven both by bacteriophages and the host inflammatory state signifying bacterial functional plasticity and suggesting potential clinical interventions.
Competing Interest Statement
The authors have declared no competing interest.