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A 12-year-old girl complained of a painless, slightly pulsatile abdominal lump for two months. Radiological imaging showed a fusiform lesion within the abdominal wall, between the external and internal oblique muscle, with nonhomogeneous echo-structure and high vascular density at the colour-power-Doppler analysis. The findings suggested an intramuscular arteriovenous malformation. The patient underwent a two-step treatment, namely a preoperative transarterial angioembolization of the nourishing vessels through the right femoral artery that was followed by a surgical resection of the lesion. Recovery was uneventful and during the follow-up no relapses were reported.

We studied the prevalence of functional abdominal pain disorders (FAPDs) and functional constipation (FC) in a large prospective cohort of children with celiac disease on a strict gluten-free diet (GFD).We performed a prospective cohort study, from 2016 through 2018, in a tertiary care center in Italy, of 417 patients (37% male; mean age, 13.7 y) with a diagnosis of celiac disease (European Society for Paediatric Gastroenterology Hepatology, and Nutrition criteria) who had been on a strict GFD for more than 1 year and had negative results from serologic tests after being on the GFD. Parents and children (10 y) were asked to fill in a questionnaire on pediatric gastrointestinal symptoms, according to Rome IV criteria. Patients' closest siblings (or cousins) who had negative results from serologic test for celiac disease were used as controls (n = 373; 39% male; mean age, 13.5 y).We found a higher prevalence of FAPDs among patients with celiac disease (11.5%) than controls (6.7%) (P.05); the relative risk (RR) was 1.8 (95% CI, 1.1-3.0). Irritable bowel syndrome (IBS) and FC defined by the Rome IV criteria were more prevalent in patients with celiac disease (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P.05 and P.001, respectively); the RR for IBS was 2.3 (95% CI, 1.1-4.6) and the RR for functional constipation was 2.1 (95% CI, 1.4-3.2). We found no differences in the prevalence of other subtypes of FAPDs. A logistic regression showed that younger age (P.05) and a higher level of anti-transglutaminase IgA at diagnosis (P.04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration.Celiac disease is associated with an increased risk of IBS and FC. Strategies are needed to manage IBS and FC in patients with celiac disease.

During the past decades, scientists have discovered the intimate role of the gut microbiome in human health, and since then, several papers have been published to investigate if the use of biotics (probiotics, prebiotics, synbiotics, and postbiotics) may have a beneficial impact on human health both in treatment and prevention. We now ask ourselves whether we have reached the finish line or just a new starting point, as the evidence supporting the use of biotics in several still needs a lot of work. Many questions remain unanswered today because the evidence differs depending on the indication, used strain, and amount and duration of administration. Herein we will summarize the evidence on probiotics in some gastrointestinal diseases such as infantile colic, functional abdominal pain disorders, celiac disease, acute gastroenteritis, inflammatory bowel disease, and Helicobacter Pylori infection.

Adequate complementary feeding practices are important for short- and long-term child health. In industrialized countries, the formulation of several commercial baby foods (CBFs) and an increase in their consumption has been noticed. Aim: To update and analyze the nutritional composition of CBFs available in the Italian market. Methods: Data collection carried out in two steps (July 2018–January 2019) and updated in May–September 2021. The information on CBFs was taken from the websites of the major CBF producers available in Italy. The collected information were: Suggested initial and final age of consumption; Ingredients; Energy value; Macronutrients (protein, lipids, and carbohydrates); Fiber; Micronutrients (sodium, iron, and calcium); Presence of salt and added sugars, flavorings, and other additives. Results: Time-space for which CBFs are recommended starts too early and ends too late; protein content is adequate and even too high in some food; Amount of fats and their quality must be improved, keeping the intake of saturated fats low; Sugar content is too high in too many CBFs and salt is unnecessarily present in some of them. Finally, the texture of too many products is purée, and its use is recommended for too long, hindering the development of infants’ chewing abilities.

Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal–oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-07158-0.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multifactorial etiology, characterized by impairment in two main functional areas: (1) communication and social interactions, and (2) skills, interests and activities. ASD patients often suffer from gastrointestinal symptoms associated with dysbiotic states and a “leaky gut.” A key role in the pathogenesis of ASD has been attributed to the gut microbiota, as it influences central nervous system development and neuropsychological and gastrointestinal homeostasis through the microbiota–gut–brain axis. A state of dysbiosis with a reduction in the Bacteroidetes/Firmicutes ratio and Bacteroidetes level and other imbalances is common in ASD. In recent decades, many authors have tried to study and identify the microbial signature of ASD through in vivo and ex vivo studies. In this regard, the advent of metabolomics has also been of great help. Based on these data, several therapeutic strategies, primarily the use of probiotics, are investigated to improve the symptoms of ASD through the modulation of the microbiota. However, although the results are promising, the heterogeneity of the studies precludes concrete evidence. The aim of this review is to explore the role of intestinal barrier dysfunction, the gut–brain axis and microbiota alterations in ASD and the possible role of probiotic supplementation in these patients.

During the pandemic of SARS-Cov-2, among other clinical and public health issues, a major concern raised by SARS-CoV-2 is the possibility of transmission of the infection from mother to child in the perinatal period. This has placed a question mark on the safety of breastfeeding, with ambiguity on the joint management of SARS-CoV-2 positive or suspected mothers and their children. It was aimed to evaluate breastfeeding rates for newborns of asymptomatic SARS-CoV-2 positive mothers who were temporarily separated from their babies at birth, compared to those who were not separated.Babies who were not isolated from their mothers at delivery were significantly more likely to be breastfed and were at no higher risk of infection with SARS-CoV-2.Following the World Health Organization (WHO) recommendations and strict hand and mask hygiene measures, breastfeeding practices can be established and maintained through rooming-in, thus promoting the mother-child bond without compromising the safety of the newborn.

Several metabolomics-based studies have provided evidence that autistic subjects might share metabolic abnormalities with gut microbiota dysbiosis and alterations in gut mucosal permeability. Our aims were to explore the most relevant metabolic perturbations in a group of autistic children, compared with their healthy siblings, and to investigate whether the increased intestinal permeability may be mirrored by specific metabolic perturbations. We enrolled 13 autistic children and 14 unaffected siblings aged 2–12 years; the evaluation of the intestinal permeability was estimated by the lactulose:mannitol test. The urine metabolome was investigated by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The lactulose:mannitol test unveiled two autistic children with altered intestinal permeability. Nine metabolites significantly discriminated the urine metabolome of autistic children from that of their unaffected siblings; however, in the autistic children with increased permeability, four additional metabolites—namely, fucose, phenylacetylglycine, nicotinurate, and 1-methyl-nicotinamide, strongly discriminated their urine metabolome from that of the remaining autistic children. Our preliminary data suggest the presence of a specific urine metabolic profile associated with the increase in intestinal permeability.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. Methods: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia, at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. Results: A total of 465 children (M 42% mean age 7.1 years (range: 1–16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54–2.9%). Only one child was diagnosed as eosinophilic esophagitis, we calculated a prevalence of 0.3% (95% CI: 0.2–0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89–47.7%, p = 0.06) than in the general population. Conclusion: The finding of an increased number of eosinophils (&gt, 15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

Goals:The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD).Background:About 30% of patients with CD adherent to a GFD suffer from IBS-type

This work aimed to define the microbial consortia that are able to digest gluten into non-toxic and non-immunogenic peptides in the human gastrointestinal tract. Methods: 131 out of 504 tested Bacillus and lactic acid bacteria, specifically Bacillus (64), lactobacilli (63), Pediococcus (1), and Weissella (3), showed strong gastrointestinal resistance and were selected for their PepN, PepI, PepX, PepO, and PepP activities toward synthetic substrates. Based on multivariate analysis, 24 strains were clearly distinct from the other tested strains based on having the highest enzymatic activities. As estimated by RP-HPLC and nano-ESI–MS/MS, 6 cytoplasmic extracts out of 24 selected strains showed the ability to hydrolyze immunogenic epitopes, specifically 57–68 of α9-gliadin, 62–75 of A-gliadin, 134–153 of γ-gliadin, and 57–89 (33-mer) of α2-gliadin. Live and lysed cells of selected strains were combined into different microbial consortia for hydrolyzing gluten under gastrointestinal conditions. Commercial proteolytic enzymes (Aspergillusoryzae E1, Aspergillusniger E2, Bacillussubtilis Veron HPP, and Veron PS proteases) were also added to each microbial consortium. Consortium activity was evaluated by ELISA tests, RP-HPLC-nano-ESI–MS/MS, and duodenal explants from celiac disease patients. Results: two microbial consortia (Consortium 4: Lactiplantibacillus (Lp.) plantarum DSM33363 and DSM33364, Lacticaseibacillus (Lc.) paracasei DSM33373, Bacillussubtilis DSM33298, and Bacilluspumilus DSM33301, and Consortium 16: Lp. plantarum DSM33363 and DSM33364, Lc. paracasei DSM33373, Limosilactobacillusreuteri DSM33374, Bacillusmegaterium DSM33300, B.pumilus DSM33297 and DSM33355), containing commercial enzymes, were able to hydrolyze gluten to non-toxic and non-immunogenic peptides under gastrointestinal conditions. Conclusions: the results of this study provide evidence that selected microbial consortia could potentially improve the digestion of gluten in gluten-sensitive patients by hydrolyzing the immunogenic peptides during gastrointestinal digestion.

Background: non-autoimmune thyroid disorder is a common finding in celiac patients, more frequent than in the general population. An impairment of iodine absorption has been hypothesized, but it has never been investigated so far. We aimed to evaluate the iodine absorption in children and adolescents with newly diagnosed celiac disease. Methods: 36 consecutive celiac patients (age 7.4 years, range 2.4–14.5 years) before starting a gluten-free diet (GFD) were enrolled. We assayed the urinary iodine concentration (UIC) in a 24-h urine sample, at baseline (T0) after 3 (T1) and 12 months (T2) of GFD. Results: UIC at T0 was 64 μg/L (IQR 45–93.25 μg/L) with an iodine deficiency rate of 77.8%. UIC was not different according to histological damage, clinical presentation (typical vs atypical), we found no correlation with the thyroid function tests and auxological parameters. UIC was not statistically different at T1 (76 μg/L) and T2 (89 μg/L) vsT0. UIC at T2 was similar between patients with positive and negative anti-transglutaminase antibodies at T2. No patients presented overt hypothyroidism during the study. Conclusions: We found that iodine absorption in celiac children is impaired compared to the general population, it increases slightly, but not significantly, during the GFD. We should regularly reinforce the need for a proper iodine intake in celiac disease patients to reduce iodine deficiency risk.

Celiac Disease (CD) is an autoimmune enteropathy caused by exposure to gluten in genetically predisposed people. While gluten is the main driving force in CD, evidence has shown that microbiota might be involved in the pathogenesis, development, and clinical presentation of CD. Microbiota manipulation may modify its functional capacity and may be crucial for setting-up potential preventive or therapeutic application. Moreover, probiotics are an excellent source of endopeptidases for digesting gluten.In this narrative review we illustrate all the recent scientific discoveries in this field including CD pathogenetic mechanism where gut microbiota might be involved and possible use of probiotics in CD prevention and treatment.In the future, probiotics could be used as an add-on medication for strengthening/facilitating the gluten-free diet (GFD) and improving symptoms; the prospect of using it for therapeutic purposes is to be sought in a more distant future.

Background. To date, there is no reliable marker for the diagnosis of non-celiac gluten sensitivity (NCGS), which benefits from a gluten-free diet (GFD). This condition is characterized by functional gastrointestinal symptoms similar to those occurring in the course of irritable bowel syndrome (IBS). However, IBS has a higher prevalence, and often benefits from the administration of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. The overlap of symptoms between these two pathologies has led to an overestimation of self-made diagnosis NCGS. Aims. To better identify NCGS in subjects with a previous diagnosis of IBS. Methods. All subjects received a low FODMAP diet that was also gluten-free (low FODMAP-GFD), and those presenting an improvement of symptoms were exposed to gluten or placebo (double-blind challenge with wash-out and crossover). The response to dietary treatments was evaluated by visual analogue scale (VAS). Results. Of 30 patients (23 women, seven men, aged 42.2 &plusmn, 12.5 years, body mass index (BMI ) 24.7 &plusmn, 4.1 kg/m2), 26 benefited from the administration of low FODMAP-GFD and were exposed to the gluten/placebo challenge. After the challenge, using an increase of visual analogue scale VAS (&Delta, VAS) &ge, 30%, 46.1% of the patients were NCGS+. However, this percentage became only 19.2% using a different method (mean ∆-VAS score plus two standard deviations). Conclusions. FODMAP intolerance could hide the response to a challenge test with gluten for the identification of NCGS in IBS patients. A low FODMAP-GFD followed by gluten/placebo challenge is able to identify patients with NCGS better. ClinicalTrials.gov registration number NCT04017585.

The symbiotic relationship between microbes and human is fundamental for a physiological development and health. The microbiome of the newborn undergoes to dramatic changes during the process of birth and in the first thousand days of life. Mother Nature provided us with the best possible start to achieve eubiosis: vaginal delivery to receive our mother’s microbiome and breast milk that favours the establishment of beneficial bacteria. Infants deprived of one or both of these evolutionary gifts undergo to important modification of the microbial communities leading to a state of dysbiosis enhancing the chance of the emergence of a variety of immune, inflammatory and metabolic disorders. Are we able to imitate nature? Is there any intervention for dysbiosis in children born by cesarean section? In this review we will try to answer to this intriguing question on the basis of the most recent scientific evidences.

Background/Aims Combined multichannel intraluminal impedance and pH monitoring (MII/pH) is considered the most accurate test to detect gastroesophageal reflux (GER), however lacking reference values. We aim to determine reference values for the pediatric population and to correlate these values with age and postprandial/fasting period. Methods We evaluated MII/pH traces from patients (newborns, infants, and children) admitted to 3 Italian hospitals and who underwent MII/ pH for suspected GER disease. Patients with MII/pH traces that showed significant symptom-reflux associations and/or a pathological reflux index (> 6% for newborns and infants, > 3% for children) were excluded. Traces were analysed in their entirety, and in the postprandial period (first hour after a meal) and the fasting period (the following hours before the next meal) separately. Results A total of 195 patients (46 newborns, 83 infants, and 66 children) were included. Age positively correlated with frequency of acidic GER events (r = 0.37, P < 0.05) and negatively associated with weakly acidic GER events (r = 0.46, P < 0.05). Conclusions This study describes the distribution of MII/pH values in a pediatric population with normally acidic GER exposure and no significant association between GER events and symptoms. These MII/pH values may be used as reference values in clinical practice for a corrected GER disease diagnosis in the pediatric population. (J Neurogastroenterol Motil 2020;26:370-377)

Multichannel intraluminal impedance pH (MII-pH) monitoring currently represents the gold standard diagnostic technique for the detection of gastro-esophageal reflux (GER), since it allows to quantify and characterize all reflux events and their possible relation with symptoms. Over the last ten years, thanks to its strengths and along with the publication of several clinical studies, its worldwide use has gradually increased, particularly in infants and children. Nevertheless, factors such as the limited pediatric reference values and limited therapeutic options still weaken its current clinical impact. Through an up-to-date review of the available scientific evidence, our aim was to produce a position paper on behalf of the working group on neurogastroenterology and acid-related disorders of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) on MII-pH monitoring technique, indications and interpretation in pediatric age, in order to standardise its use and to help clinicians in the diagnostic approach to children with GER symptoms.

OBJECTIVE: The clinical relevance of esophageal baseline impedance (BI) remains to be determined. In the present study, we explored the impact of gastroesophageal reflux disease (GERD) and esophageal dysmotility on BI. METHODS: A total of 18 children with esophageal atresia, 26 children with GERD, and 17 controls prospectively underwent esophagogastroduodenoscopy and pH-impedance monitoring. BI was measured in both proximal and distal esophagus. Gastroesophageal reflux (GER) and bolus transit indicators were defined according to published criteria. RESULTS: Patients with esophageal atresia showed significantly lower proximal and distal BI values (952 [716-1811] Ω; 895 [284-1189] Ω; respectively) compared with those with GERD (3015 [2368-3975] Ω; 2231 [1770-3032] Ω, P < 0.001 and

OBJECTIVE In children with type 1 diabetes mellitus (T1DM), elevated levels of antitissue transglutaminase (anti-tTG) antibody may spontaneously normalize, despite continued consumption of gluten. We aimed to investigate the prevalence of spontaneous normalization of anti-tTG levels and the existence of factors predictive for this outcome. RESEARCH DESIGN AND METHODS All children referred from 2002 to 2012 were screened for celiac disease (CD) at diabetes onset and at specific intervals. In the presence of a high anti-tTG titer or clinical symptoms, children were offered endoscopy, and asymptomatic patients with a low anti-tTG titer were invited to a second serological test after 6 months of eating a gluten-containing diet. RESULTS The study included 446 children. Of these, 65 (14.5%) became positive for celiac serology: 38 (58%) had a persistently elevated anti-tTG titer and 27 (41%) fluctuating anti-tTG titer; 18 (28%) became negative. The prevalence of positive CD autoimmunity and overt CD was 14.3% (95% CI 11–17) and 8.5% (95% CI 5–10), 15- and 8-times higher than the general pediatric population, respectively. Asymptomatic children older than 9.1 years at T1DM onset had the lowest risk to develop CD. CONCLUSIONS Serum anti-tTG levels decreased spontaneously in 40% of children with T1DM and became negative in 20%, despite gluten consumption. This finding supports the hypothesis of a state of temporary positivity of celiac serology in children with diabetes. In absence of clinical symptoms or signs of CD, histological confirmation of the disease and the gluten-free diet should be postponed to avoid unnecessary procedures and reduce an additional psychological burden.

Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra-intestinal symptoms that are related to the ingestion of gluten in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). In this multicenter study, we aim for the first time to evaluate the prevalence of NCGS in pediatric subjects with chronic functional gastrointestinal symptoms associated with gluten ingestion using a double-blind placebo-controlled (DBPC) gluten challenge with crossover.Among 1,114 children with chronic gastrointestinal symptoms (negative CD and WA), those exhibiting a positive correlation between symptoms and gluten ingestion were eligible for a diagnostic challenge including the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge. Patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.Out of 1,114 children, 96.7% did not exhibit any correlation with gluten ingestion. Thirty-six children were eligible; after the run-in and open GFD, 28 patients entered the gluten challenge. Eleven children (39.2%; 95% CI: 23.6-53.6%) tested positive.This is the first demonstration of the existence of NCGS in children that reinforce the need for a DBPC for the diagnosis as the diagnosis is ruled out in60% of cases. The registration identifier in ClinicalsTrials.gov is NCT02431585.

Non-celiac gluten sensitivity (NCGS) is a condition in which symptoms are triggered by gluten ingestion, in which both allergic and autoimmune mechanisms have been ruled out. The “classical” presentation of NCGS is a combination of gastrointestinal symptoms (including abdominal pain, bloating, and bowel habit abnormalities) and extra-intestinal manifestations. So far, NCGS has been described extensively in adults, and few data are available for the pediatric population. Due to lack of a serological or histological marker, the diagnosis of NCGS remains clinical and it is based on the exclusion of celiac disease and wheat allergy and on gluten challenge. G is a 2.5-year-old child referred to our Center for chronic diarrhea, diurnal abdominal pain, and mild failure to thrive. His mother reported that symptoms were related to wheat ingestion and that resolved on a gluten-free diet; therefore, she was worried about Celiac Disease. However, blood tests did support neither celiac disease because of anti-transglutaminase-IgA, anti-endomysium, and anti-gliadin-IgA negativity nor wheat allergy for the absence of specific IgE for wheat or gluten. G was positive just to anti-gliadin-IgG. We reassured the mother and concluded for a chronic unspecific diarrhea to be treated conservatively without elimination diets. On the follow-up visit, G was still complaining with same symptoms, and his growth was further slowing; we ,therefore, decided to repeat the blood tests (with similar results), to define the HLA status (DQ1/7), and to perform intestinal duodenal biopsies. These showed normal villous architecture and a modest increase of intraepithelial lymphocytes. Based on the clear association between clinical symptoms and wheat ingestion, the final diagnosis was “non IgE-mediated adverse reaction to wheat,” although G had no other clue to support this diagnosis such as personal or family history of atopy and/or eczema. G was started on a gluten-free diet with resolution of symptoms. This diagnosis was confirmed 6 months later with a double-blind placebo-controlled challenge that resulted in the onset of diarrhea and abdominal pain 30 h after wheat ingestion. This was happening in 2006 and 2 years later a “new” disease entity might have better explained the symptoms of this child: NCGS.

Gastroesophageal reflux (GER) refers to retrograde movement of gastric contents out of the stomach with or without regurgitation and vomiting.

Epigenetic modifications are among the most important mechanisms by which environmental factors can influence early cellular differentiation and create new phenotypic traits during pregnancy and within the neonatal period without altering the deoxyribonucleic acid sequence. A number of antenatal and postnatal factors, such as maternal and neonatal nutrition, pollutant exposure, and the composition of microbiota, contribute to the establishment of epigenetic changes that can not only modulate the individual adaptation to the environment but also have an influence on lifelong health and disease by modifying inflammatory molecular pathways and the immune response. Postnatal intestinal colonization, in turn determined by maternal flora, mode of delivery, early skin-to-skin contact and neonatal diet, leads to specific epigenetic signatures that can affect the barrier properties of gut mucosa and their protective role against later insults, thus potentially predisposing to the development of late-onset inflammatory diseases. The aim of this review is to outline the epigenetic mechanisms of programming and development acting within early-life stages and to examine in detail the role of maternal and neonatal nutrition, microbiota composition, and other environmental factors in determining epigenetic changes and their short- and long-term effects.

Achalasia is a rare esophageal motility disorder: its optimal treatment in children is still a matter of debate. Records of children treated for achalasia, over an 18-year period, were reviewed.Forty-eight children (median age at diagnosis 10 years; range 3-17 years) were identified. Twenty-eight patients were initially treated with Heller's myotomy (HM) and 20 with balloon dilatation (BD). At last follow-up (median 3 years; range 1-5.5 years), 43.8% (21/48) of children were symptom free. The number of asymptomatic children was significantly higher among those treated initially with HM compared to BD (HM 15/28, 53.6% BD 6/20, 30%, p 0.05). All children who underwent BD required HM due to symptom recurrence. The median (range) total number of procedures was significantly higher in the BD group (BD 3 (1-7); HM 1 (1-5); p 0.05) with a shorter time to the second intervention (BD 14 months, 95%CI 4-24; HM 58 months, 95%CI 38-79; p 0.05). Of 108 procedures, esophageal perforation occurred in two children after HM (two out of 48 HM procedures in total, 4%) and one child after BD (1/60, 1.7%).Less than half of children with achalasia are symptom free after initial treatment with either BD or HM. HM, however, when performed as first procedure, provided longer symptom-free period and reduced need for subsequent intervention. What is Known: • Balloon dilatation (BD) and Heller's myotomy (HM) are safe and effective treatment options for achalasia. • Controversy, however, exists regarding the most effective initial therapeutic approach. What is New: • HM with or without fundoplication may represent the initial therapeutic approach of choice. • Initial BD may negatively affect the outcome of a subsequent HM.

To report the indications and/or recommendations by Societies and Institutions for the use of probiotics and prebiotics in functional intestinal disorders in childhood.A position by Societies and Institutions is available only for infant colic, irritable bowel syndrome and constipation. Supplementation with the probiotic L reuteri DSM 17938 in breastfed term infants with colic appears to be effective in reducing crying, while still debated is its role in the prevention of colic. Irritable bowel syndrome is a common disorder in children and at present no specific treatments are available; existing data show that although high-quality studies are still needed, some evidence support the efficacy of LGG and VSL#3 in paediatric IBS. At present there is no evidence for the use of pre- or probiotics in childhood constipation.Probiotics in a near future may have a definite role is some FGIDs of infants and children. The main limitations for the recommendation by Societies and Institutions are the methodological issues that limit the quality of the evidence and the heterogeneity of treatments (probiotic strain and dose, mode, dose and duration of supplementation, primary outcomes, etc). Some specific strains are promising for infant colic (L. reuteri DSM 17938) and irritable bowel syndrome (LGG) while at present there is no indication for their use in the treatment of childhood constipation.

It has been suggested that sourdough fermented products have beneficial health effects. Fungal proteases and selected sourdough lactic acid bacteria were used to produce wheat bread and pasta with a reduced-gluten content (&lt, 50% of traditional products). Fermentable oligo-, di- and mono- saccharides and polyols and amylase/trypsin inhibitors were also evaluated. The sensorial features of new products were similar to traditional ones. The efficacy of these new products in reducing the severity of symptoms in Irritable Bowel Syndrome (IBS) patients were compared to traditional bread and pasta using a randomized, crossover-controlled trial. While on a strict gluten-free diet, patients were randomized to consume a reduced- or normal-gluten diet for 2weeks, then, patients from both arms started the wash-out period of one week, and subsequently started the final 2-week period on a normal or reduced-gluten diet. Compared to normal-gluten content, the administration of a reduced-gluten content diet resulted in a decrease of the Visual Analogue Scale score (p = 0.042), while no differences were found in the IBS-Severity Score, Hospital Anxiety and Depression Scale, and IBS-Quality of Life. Data herein reported are novel encouraging findings that should spur a new avenue of research aiming to develop products specifically designed for IBS patients.

Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts' recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

Background Aprepitant (Emend, Merck Sharp & Dohme Ltd, Haarlem, the Netherlands), a neurokinin-1 receptor antagonist, prevents vomiting in a range of conditions. No data are available on its use in children with cyclical vomiting syndrome (CVS). Aim We investigated the efficacy of aprepitant as prophylactic treatment or acute intervention in CVS children refractory to conventional therapies. Methods Forty-one children (median age: 8 years) fulfilling NASPGHAN criteria treated acutely (RegA) or prophylactically (RegP) with aprepitant were retrospectively reviewed. Primary outcome was the clinical response (decrease in frequency and intensity of CVS episodes). Secondary outcomes were: number of CVS episodes/year, number of hospital admissions/year, CVS episode duration, number of vomits/h, symptom-free interval length (days), and school attendance percentage. The follow-up period was 18-60 months. Results Sixteen children received RegP and 25 RegA. One child on RegP stopped treatment due to severe migraine. At 12-months on intention-to-treat analysis, 13 children on RegP (81%) achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response. On RegA, 19 children (76%) had either complete (3/25, 12%) or partial (16/25, 64%) response (P = 0.8 vs. RegP). In both RegP and RegA, there was a significant decrease in CVS episodes/year, hospital admission number/year, CVS episode length, number of vomits/h, as well as an increase in symptom-free interval duration and school attendance percentage. Side effects were reported only in RegP (5/16, 31%) including hiccough (3/16, 19%), asthenia/fatigue (2/16, 12.5%), increased appetite (2/16, 12.5%), mild headache (1/16, 6%) and severe migraine (1/16, 6%). Conclusion Aprepitant appears effective for both acute and prophylactic management of paediatric cyclical vomiting syndrome refractory to conventional therapies.