Do advanced glycation end products contribute to food allergy?

Sugars can bind non-enzymatically to proteins, nucleic acids or lipids and form compounds called Advanced Glycation End Products (AGEs). Although AGEs can form in vivo, factors in the Western diet such as high amounts of added sugars, processing methods such as dehydration of proteins, high temperature sterilisation to extend shelf life, and cooking methods such as frying and microwaving (and reheating), can lead to inordinate levels of dietary AGEs. Dietary AGEs (dAGEs) have the capacity to bind to the Receptor for Advanced Glycation End Products (RAGE) which is part of the endogenous threat detection network. There are persuasive epidemiological and biochemical arguments that correlate the rise in food allergy in several Western countries with increases in dAGEs. The increased consumption of dAGEs is enmeshed in current theories of the aetiology of food allergy which will be discussed.

Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA L74 on human enterocytes.

Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA L74 stimulated cell growth and differentiation, tight junction proteins and mucin 2 expression, and mucus layer thickness in a dose-dependent fashion. A significant stimulation of HBD-2 and LL-37 synthesis, associated with a modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and immune defence mechanisms through a direct interaction with the enterocytes. These effects could be involved in the preventive action against infectious diseases demonstrated by this fermented product in children.

Response to infliximab is related to disease duration in paediatric Crohn's disease.

BACKGROUND: Infliximab is an effective therapy in adult patients with refractory and fistulizing Crohn's disease. Experience in children is still limited. AIM: : To evaluate the experience in 22 children and adolescents treated with infliximab with refractory and/or fistulizing Crohn's disease, and to compare duration of response in children between early Crohn's disease and late Crohn's disease. METHODS: The experience in 22 children and adolescents treated with a total of 73 infusions was evaluated retrospectively. Treatment indication was refractory Crohn's disease in 9/22 patients, fistulizing Crohn's disease in 7/22 patients and both these conditions in 6/22. All patients with refractory Crohn's disease had late Crohn's disease (> 1 year), whereas 6/13 patients with fistulas had early disease (< 1 year). RESULTS: Mean Paediatric Crohn's Disease Activity Index (PCDAI) decreased from 41.2 to 16.2 at 4 weeks (P < 0.01), and to 15.4 at 18 weeks (P < 0.01). Mean PCDAI at 18 weeks in children with early Crohn's disease and late Crohn's disease was 5.5 and 18.1, respectively (P < 0.05). Complete closure of fistulas was obtained in 5/6 children with early Crohn's disease and in 2/7 children with late Crohn's disease. Immediate adverse reactions were observed in two children. CONCLUSIONS: Infliximab is a highly effective treatment in children and adolescents with both severe refractory or fistulizing Crohn's disease. Children with early Crohn's disease have a higher chance of prolonged response to infliximab than children with late Crohn's disease.

Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea.

BACKGROUND: Acute diarrhoea is a frequent problem in children with heavy economic burden for families and society. AIM: To test the efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060, arabinogalactan and xilooligosaccharides in children with acute diarrhoea. METHODS: Double-blind, randomised, placebo-controlled trial, including children (age 3-36 m) with acute diarrhoea who were allocated to placebo or synbiotic group. Major outcome was resolution rate of diarrhoea at 72 h. Total duration of diarrhoea, daily stool outputs, stool consistency, working days lost by parents, adjunctive medications, and hospitalisation were also assessed. RESULTS: We enrolled 55 children in placebo group and 52 in synbiotic group. The two groups were similar for demographic and clinical characteristics. Resolution rate of diarrhoea at 72 h was significantly higher in synbiotic group (67%) compared to placebo group (40%, P = 0.005). Children in synbiotic group showed a significant reduction in the duration of diarrhoea (90.5 h, 78.1-102.9 vs. 109.8 h, 96.0-123.5, P = 0.040), daily stool outputs (3.3, 2.8-3.8 vs. 2.4, 1.9-2.8, P = 0.005) and stool consistency (1.3, 0.9-1.6 vs. 0.6, 0.4-0.9, P = 0.002) compared to placebo group (data expressed as mean, 95% CI). Rate of parents that missed at least one working day (41.8% vs. 15.4%, P = 0.003), rate of children that needed adjunctive medications (25.5% vs. 5.8%, P = 0.005) or hospitalisation (10.9% vs. 0%, P = 0.014) after the first 72 h of treatment, were reduced in synbiotic group. CONCLUSION: The synbiotic formulation studied is effective in children with acute diarrhoea. Australian New Zealand Clinical Trials Registry (ACTRN12611000641998).

Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease.

BACKGROUND: An accurate monitoring of mucosal inflammation is important for an effective management of patients with inflammatory bowel disease. Intestinal inflammation can be detected by faecal calprotectin level determination. AIM: To comparatively evaluate the accuracy of faecal calprotectin, clinical scores, common serum markers and endoscopy in the assessment of the severity of intestinal mucosa inflammation in children with inflammatory bowel disease. METHODS: Fifty-eight paediatric patients (mean age 13.9 years, 95% CI 2.9-14.8; male 28) with confirmed inflammatory bowel disease (26 Crohn's disease, 32 ulcerative colitis) were enrolled. Before endoscopy, all patients underwent a complete evaluation including: clinical scores, erythrocyte sedimentation rate, C-reactive protein and faecal calprotectin determination. The severity of mucosal inflammation was assessed using specific endoscopic and histologic scores. RESULTS: Faecal calprotectin showed a high correlation (r=0.655) with the histologic grade of mucosal inflammation, similar to that observed for endoscopy (r=0.699), and it resulted the most accurate tool (sensitivity 94%, specificity 64%, positive predictive value 81%, negative predictive value 87%) to detect the presence of active mucosal inflammation when compared to clinical scores and common serum markers. In patients with apparent clinical and laboratory remission the accuracy of faecal calprotectin resulted further improved (sensitivity 100%, specificity 80%, positive predictive value 67%, negative predictive value 100%). CONCLUSIONS: A more accurate assessment of the severity of mucosal inflammation can be achieved by the determination of faecal calprotectin levels compared to other common clinical and laboratory indices. This non-invasive and objective method could be particular useful in patients with apparent clinical and laboratory remission.

Diagnostic accuracy of the atopy patch test in children with food allergy-related gastrointestinal symptoms.

BACKGROUND: Little is known about the diagnostic accuracy of atopy patch tests (APT) in the clinical practice of pediatric gastroenterology. Moreover, APTs containing purified food extracts have recently become available, but their diagnostic accuracy is largely undefined. PATIENTS AND METHODS: We evaluated the diagnostic accuracy of food challenge, skin prick test (SPT), serum specific IgE determination, and APT using fresh food and commercial food extracts in parallel in children referred for suspected food allergy-related gastrointestinal symptoms. RESULTS: Eighty-nine food challenges were performed in 60 patients (38 boys, median age 23 months, range 3-48 months): 31 tested positive for cow's milk (CM), 19 for hen's egg (HE), and two for wheat. Specific immunoglobulin E (IgE) determination, and SPT, respectively, were positive in 7/31 and 14/31 of patients with cow's milk allergy (CMA), and in 7/19 and 7/19 with HE allergy. The results of APT with fresh food vs a commercial assay were (1) CM: sensitivity: 64.5%vs 6.4%, specificity 95.8%vs 95.6%, positive predictive value (PPV) 95.2%vs 66.6% and negative predictive value (NPV) 67.6%vs 43.1%; (2) HE: sensitivity 84.2%vs 5.2%, specificity 100%vs 100%, PPV 100%vs 100% and NPV 75.0%vs 33.3%. CONCLUSIONS: Atopy patch test is a useful tool in the diagnostic work up of children with food-allergy-related gastrointestinal symptoms. The diagnostic accuracy of ATP was higher with fresh food than with commercial food extracts.