Increased Anti‐Flagellin and Anti‐Lipopolysaccharide Immunoglobulins in Pediatric Intestinal Failure

Abstract

Background Central line–associated bloodstream infections (CLABSIs) pose a significant challenge in the lives of patients with intestinal failure (IF). We hypothesized that plasma immunoglobulins against flagellin (FLiC) and lipopolysaccharide (LPS) would be able to differentiate CLABSIs from nonbacterial febrile episodes and that levels would increase with infection and decline following appropriate antibiotic treatment. Materials and Methods Patients with IF, due to short bowel syndrome, between the ages of 3 months and 4 years of age, were recruited at Cincinnati Children’s Hospital Medical Center. Anti-FLiC and anti-LPS plasma antibody levels were measured in 13 children with IF at baseline, during febrile events, and also following treatment with antibiotics. These were also measured in 11 healthy children without IF who were recruited as controls. Results Plasma anti-FLiC IgA levels increased during febrile episodes in all patients with IF (baseline mean of 1.10 vs febrile episode mean of 1.32 optical density units, respectively; P = .046). Neither plasma anti- FLiC nor anti-LPS IgA or IgG levels distinguished CLABSI from nonbacterial febrile episodes compared with baseline levels. Compared with controls, patients with IF had significantly higher plasma levels of anti-FLiC and anti-LPS IgA at baseline. Conclusion Plasma anti-FLiC IgA antibody levels rise during febrile episodes but do not differentiate between nonbacterial febrile illnesses and CLABSIs in pediatric IF. However, the upregulation of these antibodies in IF suggests the baseline systemic presence of Gram-negative bacterial products.

Serum Unconjugated Bile Acids and Small Bowel Bacterial Overgrowth in Pediatric Intestinal Failure: A Pilot Study

“…It is possible that prior exposure to prophylactic antibiotic use in a cyclic pattern leads to dysbiosis in the gut microbial community, which may alter the balance of microbes that are able to deconjugate luminal bile acids. We have previously published some of these possible influences …”

“…We have previously published some of these possible influences. 8,25 The synthesis, regulation, and enterohepatic recycling of bile acids is a complex process that relies partially on multiple anatomic checkpoints, liver function, gut microbiota composition, and available receptors. 22,26 Furthermore, intestinal resection (namely, of the ileum) does not appear to have the same effect on bile acid synthesis in children as has been found in adults.…”

Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis

“…The advantage of our SBR model is that it does not involve PN, thereby eliminating multiple confounding variables of PN including rates of glucose infusion, amino acid composition, different types of fat (Ω3 vs Ω6), and percent enteral intake. The significance of LPS in the context of massive SBR has been established as circulating anti-LPS immunoglobulins have been found to be elevated in human patients with short bowel syndrome(18, 19). Further, administration of LPS to rats after SBR has been shown to result in impaired structural adaptation and increased late mortality(20).…”

Circulating Biomarkers of Gut Barrier Function: Correlates and Nonresponse to Calcium Supplementation among Colon Adenoma Patients

“…One possible explanation is that obese individuals may have different gut microbiota and/or gut microbiome patterns (31); for example, obese individuals often consume a high-fat diet, which may favor the growth of gram-negative bacteria in the gut (32). Gram-negative bacteria may have a greater ability to translocate across the gut mucosa into the circulation compared to gram-positive microbes (33). Furthermore, LPS is a major component of the outer membrane of Gram-negative bacteria.…”