Background: This study explores how a child's celiac disease (CD) influences the daily life

OBJECTIVES:Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.METHODS:Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.RESULTS:The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).CONCLUSIONS:A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.

SummaryThe cytokine pattern of T lymphocytes has not been characterized in children with combinations of paediatric immunological disorders. We describe cytokine secretion in children with type 1 diabetes, coeliac disease and allergy and combinations of two of these diseases after stimulation with 'disease-specific' antigens. Peripheral blood mononuclear cells (PBMC) were collected from 68 children with type 1 diabetes, allergy or coeliac disease, two of these diseases in combination or none of these diseases. Using the enzyme-linked immunospot (ELISPOT) technique, interferon (IFN)-g and interleukin (IL)-4 were analysed from fresh PBMC spontaneously and after in vitro stimulation with antigens associated with one or more of these diseases (insulin, gluten, birch and cat extract, b-lactoglobulin, ovalbumin and phytohaemagglutinin) in order to divide T helper (Th)1-from Th2-like lymphocytes. Stimulation with birch and cat extract caused increased IL-4 secretion in allergic children. A low IFN-g response to insulin was found in type 1 diabetic children, whereas allergic children responded to insulin by increased IL-4 secretion. Children suffering from both type 1 diabetes (Th1-prone) and allergy (Th2-prone) reacted distinctly to general mitogen stimulation. Children suffering from two Th1-dominated diseases (type 1 diabetes and coeliac disease) showed hardly any response to either food or inhalation allergens. Our results indicate an important interplay between common immunological diseases in children. The combination of two Th1-deviated diseases is associated with a suppressed immune response, whereas a combination of Th1-and Th2-dominated diseases appears to increase the general immune response.

Background Dysbiosis, that is, disturbed gut microbial balance, is well documented in Crohn’s disease (CD). We aimed at studying CD-linked dysbiosis in children by analyzing fecal microbe-associated characteristics, previously not reported in children. Methods This observational study included 28 children with active CD and healthy controls. We assessed the following three indicators of gut microbiota metabolism in the feces: the presence of tryptic activity, the conversion of cholesterol to coprostanol, and the conversion of bilirubin to urobilinogen. Results The fecal tryptic activity was significantly higher in children with active CD compared to the control group (P < 0.01). The fecal coprostanol of the CD children was close to zero and differed significantly from the controls (P < 0.001). Furthermore, the children with CD had very low fecal urobilinogen, differing significantly from the control group (P < 0.001). Conclusions The significant differences in levels of fecal bacterial metabolites in patients with active CD compared to healthy controls reflect major perturbation of gut microbial functions and have not previously been reported in children. This fits well with the prevailing concept of a dysbiotic gut microbiota in CD and may have important clinical implications by bringing the dysbiosis back into balance.

T o the Editor: In their excellent overview, de Zoeten et al (1) present detailed and practical guidelines for the diagnosis and treatment of perianal Crohn disease (CD) in children. In the section on enteral therapy (page 406), they refer to a report of successful treatment with enteral nutrition in 3 children with perianal CD (2). Exclusive enteral nutrition (EEN) is a wellestablished and effective treatment in pediatric CD (3). Although the mode of action of EEN is not fully understood, modulation of the gut microflora activity in a less inflammatory direction has been proposed to be a probable explanation (4-6).Further evidence of a gut microflora-mediated anti-inflammatory effect of EEN in children with active CD was recently presented by us, analyzing the fecal short-chain fatty acid (SCFA) profile, which reflects the gut microfloral function (7). We showed that 6 weeks' EEN normalized the initially proinflammatory SCFA pattern, resulting in clinical remission. Interestingly, only children with active small bowel and/or colonic CD had a positive effect of the treatment. In children with active perianal CD, EEN had no positive effect on clinical status, inflammatory parameters, or SCFA pattern. Thus, our findings question the use of EEN as the treatment for perianal CD and illustrate the need for further research on the complex interactions between genetics, dietary nutrients, gut microflora metabolites, and intestinal inflammation in individuals with CD (6,8).