A45 INFLAMMATION AND INTESTINAL PERMEABILITY IN PEDIATRIC SHORT BOWEL SYNDROME Journal Articles uri icon

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abstract

  • Abstract Background Both intestinal dysbiosis and central-line associated blood stream infections (CLABSI) have been well documented in children with short bowel syndrome (SBS). Gastrointestinal microbiota prime and regulate mucosal immunity, therefore we hypothesize children with SBS may have longstanding increased intestinal permeability which could lead to mucosal inflammation and predispose to bacteremia. Aims We sought to investigate intestinal permeability as well as both intestinal and systemic activation of the inflammatory cascade in children with SBS. Methods Two cohorts of children with SBS were consented; with Group 1 including children with SBS requiring central venous catheter (CVC) for parenteral nutrition, and Group 2 including children with SBS without CVC. SBS groups were compared to three control groups including age and sex-matched children with CVC for hematologic disease (Group 3), children without a CVC (Group 4) and healthy adult controls (Group 5). To evaluate intestinal permeability, we quantified circulating bacterial products LPS and MDP through the binding of their respective receptors, TLR4 and NOD2. To determine colonic inflammation, fecal calprotectin was quantified from a single stool sample. Cytokine profiles included IFN-γ, IL-Iβ, IL-8, IL-10, IL-17, TNFα were quantified by Multiplex Immunoassay while gene expression of transcription factors FoxP3+, RORγT, TLR2, and TLR4, were determined by RNA extraction and quantitative PCR. Results 22 children were recruited in the study (Group 1 n=6, Group 2 n=6, Group 3 n=5, Group 4 n=5) as well as 10 adult control samples (Group 5). The median age of Group 1 was 67 months with a residual small intestine of 26.5cm (IQR 24.7–40) while those in Group 2 were 51 months with a residual small intestine of 55cm (IQR 31.2–89). Circulating bacterial products of LPS and MDP were not different between SBS groups and control children. Serum analysis of cytokine TNFα was significant (p<0.005) however multiple comparator analysis did not identify within group differences. Other cytokines did not differ between groups. Fecal calprotectin levels were not elevated however statistically lower in Group 1 (median 12.8mg/kg; IQR 9.3- 34.9) compared to in Group 2 (median 96mg/kg, IQR 71.6–188.2;) p <0.01. Relative quantification of RNA expression of FoxP3+, RORγT, TLR2, and TLR4 did not differ between groups. Conclusions Despite concern of compromised intestinal epithelial barrier function in children with SBS, this study did not detect differences in circulating bacterial products compared to control children as an assessment of intestinal permeability nor increased systemic inflammation. Further research is required to investigate intestinal epithelial barrier function over time and the mechanism of bacteremia in children with SBS. Funding Agencies CAGRegional Medical Associates of Hamilton

publication date

  • February 26, 2020