Graduate Student SNU Graduate School Department of Biomedical Sciences Seoul, Republic of Korea
Disclosure(s):
Eun Hye Yoon: No financial relationships to disclose
Introduction/Rationale: Clostridioides difficile colonization, defined by PCR detection of C. difficile and Toxin B genes in fecal samples, modulates the course of ulcerative colitis (UC). Colonized patients harbor the pathogen at the mucosal surface without overt infection, yet colonization may exacerbate early disease.
Methods: We applied single-cell RNA sequencing (scRNA-seq) to intestinal biopsies from 24 UC patients and integrated 5 healthy control datasets from the Human Cell Atlas, defining colonization status by PCR/ELISA detection.
Results: We hypothesized that C. difficile–driven inflammation sustains chronic colonic injury via expansion of a distinct IL1B⁺ monocyte subset. scRNA-seq revealed this subset uniquely enriched in colonized UC tissue, exhibiting gene programs related to neutrophil recruitment and leukocyte chemotaxis. We further identified a marked expansion of infiltrating inflammatory monocytes along the chemokine axis, accompanied by upregulation of CCL2, CCL3, CXCL3, and CXCL8. Trajectory analysis demonstrated that these monocytes differentiate into macrophages within the tissue, enhancing recruitment in inflamed lesions. Moreover, interactions between CCL2-expressing glial cells and monocytes were implicated in amplifying local inflammation.
Conclusion: These findings identify C. difficile–induced IL1B⁺ infiltrating monocytes as key amplifiers of innate immune recruitment and drivers of persistent inflammation in UC, providing mechanistic insights into pathogen-associated disease exacerbation.
