Dysregulated Immunity to Clostridioides difficile in IBD Patients Without a History of Recognized Infection.
Inflamm Bowel Dis
; 2023 Oct 24.
Article
in En
| MEDLINE
| ID: mdl-37874904
ABSTRACT
BACKGROUND & AIMS:
Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection.METHODS:
To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity.RESULTS:
We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin ß7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects.CONCLUSIONS:
These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.
Crohn's disease and ulcerative colitis patients with no history of Clostridioides difficile infection had dysregulated T cell immunity to C. difficile toxin B. This was significantly different from healthy control subjects but similar to noninflammatory bowel disease patients with recurrent C. difficile infection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Inflamm Bowel Dis
Journal subject:
GASTROENTEROLOGIA
Year:
2023
Type:
Article
Affiliation country:
Canada