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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.

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.

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.

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. 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.

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.

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.

s / Digestive and Liver Disease 47S (2015) e237–e276 e269 Conclusions: An increased frequency of autoimmune diseases iswell described inCD, but few studies have analysed this immunological phenomena at diagnosis: is autoimmunity positivity only an epiphenomenon at this stage? Follow up studies are needed. http://dx.doi.org/10.1016/j.dld.2015.07.135

R. Moretti 1,∗, G. Raimondi2, G. Borrelli 2, F. Indrio1, F. Cristofori3, R. Francavilla1, M. Gobetti 4, M. De Angelis4 1 Dip. Interdisciplinare di Medicina, Sez. di Pediatria, Universita di Bari, Italy 2 Scuola di Specializzazione in Pediatria, Universita di Bari, Italy 3 UOC Pediatria, P.O. Centrale Santissima Annunziata Taranto, Italy 4 Department of Soil, Plant and Food Sciences, Universita di Bari, Italy