Background
Children with inflammatory bowel disease (IBD) are disproportionally affected by recurrent Clostridioides difficile infection (rCDI). Although fecal microbiota transplantation (FMT) has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in pediatric IBD.
Methods
We performed a retrospective review of FMT at 20 pediatric centers in the United States (US) from March 2012-March 2020. Children with and without IBD were compared to determine differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared to determine predictors of success. Safety data and IBD-specific outcomes were obtained.
Results
A total of 396 pediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort (76% vs 81%, P=0.17). Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool (P=0.03), were without diarrhea prior to FMT (P=0.03), or had a shorter time from rCDI diagnosis until FMT (P=0.04). Children with a failed FMT were more likely to have clinically active IBD post-FMT (P=0.002) and 19 (13%) patients had an IBD-related hospitalization in the 3 month follow-up.
Conclusions
Based on the findings from this large US multi-center cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.
BackgroundSignaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung’s aganglionosis in humans. Penetrance of the disease is modulated by other genetic factors. Mutations affecting retinoic acid (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA and endothelin signaling pathways may interact in controlling development of the ENS.MethodsRat immunoselected ENS precursor cells were cultured with the EDNRB ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or 14 days. mRNA levels of genes related to ENS development, RA- and EDNRB-signaling were measured at 3 days. Proliferating cells and cells expressing neuronal, glial, and myofibroblast markers were quantified.ResultsCulture of isolated ENS precursors for 3 days with RA decreases expression of the endothelin-3 gene and that of its activation enzyme. These changes are associated with glial proliferation, a higher percentage of glia, and a lower percentage of neurons compared to cultures without RA. These changes are independent of EDNRB signaling. Conversely, EDNRB activation in these cultures decreases expression of RA receptors β and γ mRNA and affects the expression of the RA synthetic and degradative enzymes. These gene expression changes are associated with reduced glial proliferation and a lower percentage of glia in the culture. Over 14 days in the absence of EDNRB signaling, RA induces the formation of a heterocellular plexus replete with ganglia, glia and myofibroblasts.ConclusionsA complex endothelin-RA interaction exists that coordinately regulates the development of rat ENS precursors in vitro. These results suggest that environmental RA may modulate the expression of aganglionosis in individuals with endothelin mutations.
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