Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and Controls

Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored

Epigenetic master regulators HDAC1 and HDAC5 control pathobiont Enterobacteria colonization in ileal mucosa of Crohn’s disease patients

International audienceAdherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn's disease (CD) patients, are known to contribute to the etiopathogenesis of CD. Molecular mechanisms favoring AIEC ileal colonization have not been completely characterized yet. The aim of this study was to investigate whether epigenetic regulators histone deacetylases (HDAC) expression in intestinal epithelial cells of CD patients regulate Enterobacteria and AIEC encroachment to intestinal mucosa. HDAC were inhibited in vitro and in CEABAC10 mice to decipher their involvement in the entry of AIEC within host cells. CD ileal samples from the REMIND cohort were used to study the relationship between HDAC expression level and Enterobacteria/AIEC colonization in patients. Mice were fed a westernized diet and orally challenged with AIEC to determine the impact of diet on HDAC expression. Global level of acetylated histone H3 is higher in patients colonized by AIEC bacteria compared to patients non-colonized by Enterobacteria and HDAC inhibition-mediated H3 hyperacetylation promotes the entry of AIEC bacteria within intestinal epithelial cells. HDAC1 and HDAC5 are central and antagonistic in the regulation of AIEC entry within host cells in vitro, in mouse models and in ileal mucosa of CD patients. In mice fed a western-type diet, AIEC infection decreases HDAC1 expression, inducing H3 hyperacetylation to favor their own colonization. CD patients under a western diet are more prone to be colonized by AIEC bacteria as such a diet affects intestinal homeostasis, enables AIEC access to intestinal mucosa where they then manipulate hostepigenome to their advantage