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Published on: December 8, 2014
Microbial Shifts and Shorter Time to Bowel Resection Surgery Associated with C. difficile in Pediatric Crohn's
Jennifer Hellmann1, Heidi Andersen2, Lin Fei3
1Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati, OH, USA.
Insights
Clostridioides difficile infection in pediatric Crohn's disease patients significantly increases the risk of bowel resection surgery. This C. difficile positivity is linked to microbial shifts and reduced methionine biosynthesis, potentially driving surgical need.
Area of Science:
- Gastroenterology
- Microbiology
- Pediatric Surgery
Background:
- Clostridioides difficile infection (CDI) and colonization are prevalent in pediatric Crohn's disease (CD).
- Understanding the link between CDI and surgical outcomes in pediatric CD is crucial.
Purpose of the Study:
- To investigate the association between C. difficile positivity and bowel resection surgery in pediatric CD.
- To characterize microbial shifts related to C. difficile carriage and surgery in these patients.
Main Methods:
- Retrospective analysis of 75 pediatric CD patients for C. difficile carriage and surgery association.
- Prospective study of 70 pediatric CD patients using C. difficile testing and shotgun metagenomic sequencing.
- Microbiota analysis stratified by C. difficile carriage and surgical history.
Main Results:
- Bowel resection surgery rates were 21% without C. difficile versus 67% with (P = 0.003).
- Positive C. difficile testing within the first year of diagnosis showed a 4.4-fold increased hazard for first surgery (P = 0.00).
- Significant microbial and metabolic pathway differences were observed, with depletion of Alistipes and Ruminococcus species and reduced methionine biosynthesis in patients with both C. difficile and prior surgery.
Conclusions:
- Positive C. difficile testing in the first year of pediatric CD diagnosis is a strong predictor of earlier bowel resection surgery.
- Microbiota alterations, including depletion of beneficial bacteria and impaired methionine biosynthesis, may underlie the increased surgical risk associated with C. difficile in pediatric CD.
Background:
Clostridioides difficile infection and colonization are common in pediatric Crohn's disease (CD). Our aims were to test the relationship between C. difficile positivity and bowel resection surgery and to characterize microbial shifts associated with C. difficile carriage and surgery.
Methods:
A retrospective single-center study of 75 pediatric CD patients tested for association between C. difficile carriage and bowel resection surgery. A prospective single-center study of 70 CD patients utilized C. difficile testing and shotgun metagenomic sequencing of fecal samples to define microbiota variation stratified by C. difficile carriage or history of surgery.
Results:
The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003). From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2-16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis. Multivariable logistic regression analysis confirmed this association (odds ratio 16.2; 95% CI, 2.2-120; P = 0.006). Larger differences in microbial abundance and metabolic pathways were observed in patients with prior surgery than in those with C. difficile carriage. Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery.
Conclusions:
A positive C. difficile test during the first year after diagnosis is associated with decreased time to first bowel resection surgery in pediatric Crohn's disease. Depletion of beneficial commensals and methionine biosynthesis in patients with C. difficile carriage may contribute to increased risk for surgery.
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