Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans

<i>Campylobacter</i> enterocolitis may lead to post-infection irritable bowel syndrome (PI-IBS) and while some <i>C. jejuni</i> strains are more likely than others to cause human disease, genomic and virulence characteristics promoting PI-IBS development remain uncharacterized. We combined pangenome-wide association studies and phenotypic assays to compare <i>C. jejuni </i>isolates from patients who developed PI-IBS with those who did not. We show that variation in bacterial stress response (<i>Cj0145_phoX</i>), adhesion protein (<i>Cj0628_CapA</i>), and core biosynthetic pathway genes (biotin: <i>Cj0308_bioD</i>; purine: <i>Cj0514_purQ</i>; isoprenoid: <i>Cj0894c_ispH</i>) were associated with PI-IBS development. <i>In vitro </i>assays demonstrated greater adhesion, invasion, IL-8 and TNFα secretion on colonocytes with PI-IBS compared to PI-no-IBS strains. A risk-score for PI-IBS development was generated using 22 genomic markers, four of which were from <i>Cj1631c, </i>a putative heme oxidase gene linked to virulence. Our finding that specific <i>Campylobacter</i> genotypes confer greater <i>in vitro</i> virulence and increased risk of PI-IBS has potential to improve understanding of the complex host-pathogen interactions underlying this condition.