Clostridioides difficile (C. diff), previously known as Clostridium difficile is a relatively common gastrointestinal tract infection and has a significant association with inflammatory bowel disease (IBD). C. diff infection and the C. diff carriage state may be difficult to differentiate in patients in IBD due to similar symptoms occurring with active IBD as well as with an active C. diff infection (diarrhea, abdominal pain, etc.). The authors of this study evaluated the progression to intestinal resection in pediatric patients with IBD diagnosed with C. diff carriage within one year of IBD diagnosis, and they evaluated fecal microbiome samples in such pediatric patients in relation to C. diff carriage state as well as in relation to a history of intestinal surgery.
Patients with Crohn disease (CD) from a single tertiary children’s hospital (age 21 years old or less) were retrospectively included in the study if they had stool samples as part of that institution’s IBD Biorepository and if they had C. diff testing within one year of the CD diagnosis. At the same time, a prospective study occurred for patients who were diagnosed with CD and who subsequently could provide stool sampling. Stool samples were analyzed for calprotectin levels and had C. diff polymerase chain reaction (PCR) testing as well as microbiome sampling performed by high throughput shotgun metagenomic sequencing (rapid parallel DNA sequencing). Metabolic pathways of bacteria were analyzed using nucleotide and peptide databases.
The retrospective aspect of the study demonstrated a C. diff positivity rate of 19% in the CD group with significantly more patients with C. diff having had antibiotic exposure within 30 days of testing. Most patients with CD were in the age range of 10 to 17 years, and the percentage of steroid exposure in the first year of life was not statistically different regardless of C. diff status. The rate of intestinal resection was significantly lower for patients with negative C. diff testing (21%) compared to patients with positive C. diff testing (67%). Additionally, patients with positive C. diff testing had a shorter mean time to intestinal resection (527 days) compared to patients with negative C. diff testing (1268 days). Univariate
analysis showed that steroid or anti-tumor necrosis factor (anti-TNF) medication exposure did not change results. Multivariate analysis demonstrated that only positive C. diff testing was associated with
the need for intestinal surgery in patients with CD
The subsequent prospective study demonstrated that 14% of patients with CD had positive C. diff testing, and 9% of patients with CD had a history of intestinal surgery. Similar to the retrospective cohort, patients with positive C. diff testing were significantly more likely to have had prior intestinal surgery. There was no difference in fecal calprotectin levels or reported IBD symptoms between groups. High throughput shotgun metagenomic sequencing demonstrated no overall difference in the fecal microbiome profile between patients with or without C. diff although there was a significant decrease in 123 taxa in patients with a positive C. diff infection. These taxa tended to be commensal organisms that had a potential mucosal protective effect. Metabolic profiles were not significantly different between patients regardless of C. diff status although patients that underwent intestinal surgery had 95 metabolic pathways that were altered compared to patients who had not had surgery (such as downregulated methionine biosynthesis pathways). Finally, patients with positive C. diff testing and a history of intestinal surgery had 47 bacterial species that were significantly reduced. These taxa were associated with protective gut function.
This study appears to show that young patients with CD and positive C. diff testing are at an increased risk of intestinal resection. These patients had microbiome changes noted as well suggesting the potential loss of a protective gut microbiome. The authors theorize that the early presence of C. diff in a young person with CD may be due to significant alterations in the microbiome leading to bowel inflammation and subsequent surgery.
Hellmann J, Andersen H, Fei L, Linn A, Bezold R, Lake K, Jackson K, Meyer D, Dirksing K, Bonkowski E, Ollberding N, Haslam D, Denson L. Microbial shifts and shorter time to bowel resection surgery associated with C. difficile in pediatric Crohn’s disease.