Over the past decades, an increased importance has been given to gastrointestinal (GI) endoscopy in the management of children with inflammatory bowel diseases (IBD), considering that mucosal healing has been recognized as the optimal endpoint in the treat-to-target paradigm. The recent advances in technology and anesthesia have facilitated the comprehensive evaluation of the GI tract. In this review, we will discuss the role of ileocolonoscopy, upper GI endoscopy, and device-assisted enteroscopy in the work-up and management of pediatric Crohn's disease (CD) and ulcerative colitis, with particular attention on non-invasive endoscopic techniques, such as wireless capsule endoscopy. We will also analyze the most commonly used endoscopic scoring systems, including small bowel scoring systems and endoscopic recurrence grading of neo-terminal ileum CD. Moreover, we will focus on the endoscopic management of complications, such as strictures, that commonly require surgery. Lastly, we will discuss cancer surveillance in children with IBD, with particular consideration of the role of high-definition endoscopic equipment and chromoendoscopy in dysplasia detection rates.

Coeliac disease (CD) is an autoimmune enteropathy that primarily affects the small intestine, causing mucosal inflammation and variable villous atrophy. It occurs in genetically predisposed subjects following the ingestion of gluten, a protein complex of cereals such as wheat, barley, rye, whose main fractions are prolamins (including gliadin) and gluten [ [1] Lebwohl B. Rubio-Tapia A. Epidemiology, presentation, and diagnosis of celiac disease. Gastroenterology. 2021; 160: 63-75 Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar ]. "Per ELISA": Time to adopt anti-transglutaminase/deamidated gliadin peptide diagnostic combination in coeliac disease of adults?Digestive and Liver DiseasePreviewAnti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTg) play a pivotal role in coeliac disease (CD) diagnosis. Deamidated anti-gliadin peptides (DGP) were added to the CD diagnostic workup. Full-Text PDF

OBJECTIVE AND RATIONALE:Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, manifests with chronic intestinal inflammation and frequent sequential fibrosis. Current pharmacological therapies may show harmful side effects and are not useful for prevention or resolution of fibrosis. Thus, the use of alternative therapies is emerging as a novel useful approach. Previous results suggest that Scutellaria baicalensis Georgi (SBG) and Boswellia serrata (BS) display anti-inflammatory properties. The aim of this study was to investigate in intestinal epithelial cells and fibroblasts the anti-inflammatory and anti-fibrotic potential of SBG and BS, alone or in combination. METHODS:Human colorectal adenocarcinoma cells (HT29), human intestinal epithelial cells (HIEC6) and human colon fibroblasts (CCD-18Co) were used. Cells were pretreated with SBG and BS and then exposed to pro-inflammatory and pro-fibrotic cytokines. RESULTS:SBG and BS extracts significantly decreased pro-inflammatory cytokine expression and improved epithelial restitution in HT29 and HIEC6 cells. Besides, fibrotic marker expression, including SNAIL, ACTA2, ZNF281, was strongly reduced. Colon myofibroblasts treated with SBG and BS showed a significant decrease of fibrotic markers as well. CONCLUSIONS:SBG and BS extracts significantly reduce inflammation and impair fibrosis in intestinal epithelial cells and colon myofibroblasts. No cooperative effect is observed.

Abstract Background Celiac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis. Methods CD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts. Results CD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60–8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81–11.06]) and 62 (median age: 9.5 [IQR: 6.26–12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47–6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups. Conclusion CD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.

Microalgae are natural sources of valuable bioactive compounds, such as polyunsaturated fatty acids (PUFAs), that show antioxidant, anti-inflammatory, anticancer and antimicrobial activities. The marine microalga Isochrysis galbana (I. galbana) is extremely rich in ω3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Probiotics are currently suggested as adjuvant therapy in the management of diseases associated with gut dysbiosis. The Lactobacillus reuteri (L. reuteri), one of the most widely used probiotics, has been shown to produce multiple beneficial effects on host health. The present study aimed to present an innovative method for growing the probiotic L. reuteri in the raw seaweed extracts from I. galbana as an alternative to the conventional medium, under conditions of oxygen deprivation (anaerobiosis). As a result, the microalga I. galbana was shown for the first time to be an excellent culture medium for growing L. reuteri. Furthermore, the gas-chromatography mass-spectrometry analysis showed that the microalga-derived ω3 PUFAs were still available after the fermentation by L. reuteri. Accordingly, the fermented compound (FC), obtained from the growth of L. reuteri in I. galbana in anaerobiosis, was able to significantly reduce the adhesiveness and invasiveness of the harmful adherent-invasive Escherichia coli to intestinal epithelial cells, due to a cooperative effect between L. reuteri and microalgae-released ω3 PUFAs. These findings open new perspectives in the use of unicellular microalgae as growth medium for probiotics and in the production of biofunctional compounds.

BACKGROUND:Allergy to cow's milk is the most frequent allergy occurring in infants and young children. The dietary management of these patients consists of the elimination of any cow's milk proteins from the diet, and for formula-fed infants, the substitution of the usual infant formula with an adapted formula that is generally based on extensively hydrolyzed cow's milk proteins. The American Academy of Pediatrics has established specific criteria to confirm the hypoallergenicity of a formula intended for these children.AIM:To assess the hypoallergenicity of a new thickened extensively hydrolyzed casein-based formula (TeHCF) in children with cow's milk allergy (CMA).METHODS:Children diagnosed with CMA through a double-blind placebo-controlled food challenge (DBPCFC) were randomly administered increased doses of a placebo formula or the TeHCF [Allernova, new thickener including fibres (Novalac)] under double-blind conditions and medical surveillance on two separate days. Otherwise, both of these formulas and a cow's milk-based formula were randomly introduced to children who were highly suspected of having CMA on three separate days. Immediate and late reactions occurring after the introduction of any of these formulas were thoroughly recorded by the physician at the hospital and reported by parents to the physician after hospital discharge, respectively. If the children tolerated the TeHCF during the DBPCFC, they were exclusively fed this formula during a 3-mo period where potential allergic symptoms, anthropometric parameters, as secondary outcomes, and adverse events were registered. The Cow's Milk-related Symptoms Score (CoMiSSTM) was assessed and anthropometric parameters were compared to World Health Organization (WHO) reference data.RESULTS:Of the 30 children included in the study, the CMA diagnosis of 29 (mean age: 8.03 ± 7.43 mo) patients was confirmed by a DBPCFC. The children all tolerated the TeHCF during both the challenge and the subsequent 3-mo feeding period, which they all completed. During the latter period, the CoMiSSTM remained at a very low level, never exceeding its baseline value (1.4 ± 2.0), growth parameters were within WHO reference standards and no adverse event related to the TeHCF was reported. Over the first week of this period, the proportion of patients with digestive discomfort significantly decreased from 20.7% (6/29) to 3.4% (1/29), P = 0.025. The proportion of satisfaction with the overall effect of the formula reported by the parents and investigator was high, as was the formula acceptability by the child.CONCLUSION:The new TeHCF meets the hypoallergenicity criteria according to the American Academy of Pediatrics standards, confirming that the tested TeHCF is adapted to the dietary management of children with CMA. Moreover, growth was adequate in the included population.

Potential celiac disease (PCD) is defined by the presence of positive serum antibodies, HLA-DQ2/DQ8 haplotypes, and a normal small intestinal mucosa (Marsh grade 0-1). This condition occurs in one-fifth of celiac disease (CD) patients and usually represents a clinical challenge. We reviewed genetic, histologic, and clinical features of this specific condition by performing a systematic search on MEDLINE, Embase, and Scholar database. Accordingly, we identified different genetic features in patients with PCD compared to the classical forms. Frequently, signs of inflammation (deposits of immunoglobulin A (IgA) and/or increased number of intraepithelial lymphocytes) can be clearly identify in the mucosa of PCD patients after an accurate histological assessment. Finally, the main challenge is represented by the treatment: the gluten-free diet should be considered only in the presence of gluten-dependent symptoms in both children and adults. What is known: (i) potential celiac disease (PCD) occurs in one-fifth of all celiac diseases (CD), and (ii) despite the absence of classical lesions, clear signs of inflammation are often detectable. What is new: (i) patients with PCD show different genetic features, and (ii) the presence of gluten-dependent symptoms is the main determinant to initiate the gluten-free diet, after a complete diagnostic work-up.

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-α)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1β, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1β and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria.

Background: Krill oil is a marine derived oil rich in phospholipids, astaxanthin and omega-3 fatty acids. Several studies have found benefits of krill oil against oxidative and inflammatory damage.Aims: We aimed at assessing the ability of krill oil to reduce intestinal inflammation by improving epithelial barrier integrity, increasing cell survival and reducing pathogenicity of adherent-invasive Escherichia coli.Methods: CACO2 and HT29 cells were exposed to cytomix (TNF alpha and IFN gamma) to induce inflammation and co-exposed to cytomix and krill oil. E-cadherin, ZO-1 and F-actin levels were analyzed by immunofluorescence to assess barrier integrity. Scratch test was performed to measure wound healing. Cell survival was analyzed by flow cytometry. Adherent-invasive Escherichia coli LF82 was used for adhesion/invasion assay.Results: In inflamed cells E-cadherin and ZO-1 decreased, with loss of cell-cell adhesion, and F-actin polymerization increased stress fibres; krill oil restored initial conditions and improved wound healing, reduced bacterial adhesion/invasion in epithelial cells and survival within macrophages; krill oil reduced LF82-induced mRNA expression of pro-inflammatory cytokines.Conclusions: Krill oil improves intestinal barrier integrity and epithelial restitution during inflammation and controls bacterial adhesion and invasion to epithelial cells. Thus, krill oil may represent an innovative tool to reduce intestinal inflammation. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.