Introduction
Children with inflammatory bowel diseases (IBD) are particularly vulnerable to Clostridioides difficile infections (CDI) and experience significantly worse health outcomes including increased hospitalisation and shorter time to their first bowel resection. Previous studies have correlated these outcomes to specific gastrointestinal microbiome features. However, data regarding features that may predispose PIBD patients to CDI is lacking. Furthermore, it is not known whether CDI has long-term impacts on the microbiome of PIBD patients in remission.
Aims & Methods
Our primary aims were to investigate whether PIBD-CDI patients had a distinct microbiota at baseline compared to PIBD controls, to examine whether PIBD-CDI patients had a distinct microbiome during remission than those without CDI, and whether there were changes in their stool short chain fatty acids (SCFA) composition. Finally, we aimed to assess whether PIBD patients with CDI had worse outcome.
Patients aged 2-17 years and newly diagnosed with IBD between November 2014 and March 2019 were invited to participate. Each patient was requested to submit 4 stool samples in an interval of six months between samples and follow up continued until June 2021. Patients were divided into those that developed CDI (IBD-CDI) and those who did not (IBD controls). DNA was extracted from stool samples and the microbiota of each was profiled using 16S rRNA amplicon sequencing on an Illumina MiSeq. SCFA were quantified from the stool samples. Data analysis was further divided into 2 cohorts: Cohort 1 represented microbiome data from samples of patients who developed CDI and were collected prior to the infection. Cohort 2 represented microbiome data from samples of patients in remission who had CDI. Microbial composition and SCFAs were compared to non-CDI controls within each cohort. Hazard ratio (HR) was calculated to progression to biologic treatment and surgeries in patients who had a CDI compares to those who did not. Random forest classification model was used to predict CDI using microbial composition.
Results
Patients who had CDI were more likely to progress to a biologic therapy (HR 1.85 P =0.06) and had significantly more hospitalisations (RR 2.20, P< 0.001) and surgery (HR 3.15, P= 0.019).
Cohort 1:
Patients who did not develop CDI had higher abundance of Bifidobacterium bifidum, Blautia hydrogenotrophica, Clostridium sensu stricto 2 cadaveris, Eubacterium, Ruminococcus torques group, and Lachnoclostridium.
The Eubacterium, Blautia hydrogenotrophica, Ruminococcus torques group and Lachnoclostridium were associated with high levels of stool SCFAs.
Random forest classification model was able to predict patient who did not develop CDI.
Cohort 2:
Patients post CDI had significantly lower beta diversity.
The Oscillospirales CAG 352, NK4A214 group and UCG 002 were all less abundant in post-CDI patients, and were associated with higher SCFA production. Specifically, propionic acid (CAG 352), isovaleric and isobutyric acid (NK4A214 and UCG 002). Additionally, alistipes was associated with higher levels of isovaleric and isobutyric acids.
Conclusion
We were able to predict paediatric IBD patients that were protected from CDI based on baseline microbial composition. Paediatric IBD patients who developed CDI during the course of the disease developed more severe outcome with more surgeries and hospitalisations. They had long term changes to their microbiome.
References
Pascarella F, Martinelli M, Miele E, Del Pezzo M, Roscetto E, Staiano A. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr. 2009 Jun;154(6):854–8.
Hellmann J, Andersen H, Fei L, Linn A, Bezold R, Lake K, et al. Microbial shifts and shorter time to bowel resection surgery associated with c. difficile in pediatric Crohn’s disease. Inflamm Bowel Dis. 2020;
Sokol H, Jegou S, McQuitty C, Straub M, Leducq V, Landman C, et al. Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection. Gut Microbes. 2018;
Disclosure
No conflict of interest