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

Stephanie Peters, Ben Pascoe, et al. use whole-genome sequencing and phenotypic analysis of clinical strains from patients to identify potential genetic factors involved in irritable bowel syndrome resulting from Campylobacter jejuni infection. Their data suggest that genes involved in the bacterial stress response and biosynthetic pathways may contribute toward irritable bowel syndrome, providing further insight into links between Campylobacter genotypes and risk of disease. Campylobacter enterocolitis may lead to post-infection irritable bowel syndrome (PI-IBS) and while some C. jejuni 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 C. jejuni isolates from patients who developed PI-IBS with those who did not. We show that variation in bacterial stress response (Cj0145_phoX), adhesion protein (Cj0628_CapA), and core biosynthetic pathway genes (biotin: Cj0308_bioD; purine: Cj0514_purQ; isoprenoid: Cj0894c_ispH) were associated with PI-IBS development. In vitro assays demonstrated greater adhesion, invasion, IL-8 and TNF alpha 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 Cj1631c, a putative heme oxidase gene linked to virulence. Our finding that specific Campylobacter genotypes confer greater in vitro virulence and increased risk of PI-IBS has potential to improve understanding of the complex host-pathogen interactions underlying this condition.

Automated summary

Researchers used whole-genome sequencing and phenotypic analysis to identify potential genetic factors linked to irritable bowel syndrome caused by Campylobacter jejuni infection. They found that specific genetic variations in bacterial stress response, adhesion protein, and core biosynthetic pathway genes may contribute to the development of post-infection irritable bowel syndrome (PI-IBS). The study demonstrated that certain Campylobacter genotypes exhibit increased virulence in vitro, shedding light on the complex host-pathogen interactions underlying this condition.