SELF-REPORTED NON-CELIAC GLUTEN SENSITIVITY IN ITALIAN YOUNG ADULTS: A CROSS-SECTIONAL STUDY. A DIETARY FAD?

OBJECTIVES: In different countries, the exact prevalence of people that refer symptoms after gluten ingestion is increasing and the unavailability of reliable laboratory tests to diagnose the condition known as non-celiac gluten sensitivity (NCGS) has opened the door to the spread of survey-based studies to hypothesize a prevalence of this condition with highly discordant results. We aim to describe the attitude toward gluten consumption in a large population of young adults in Italy. METHODS: A questionnaire-based cross-sectional study was conducted in thirteen Italian cities to investigate the dietary attitudes of more than 9400 people distributed throughout the country about gluten consumption. Only those referring to gluten-related symptoms with a frequency equal to "always" or "most of the time" were considered self-reported NCGS (SR-NCGS) patients. RESULTS: Five thousand two hundred and thirty-four of 9432 eligible participants (55.5%) fully completed the questionnaire. Excluding those with previous gastrointestinal diagnoses of celiac disease and wheat allergy, we have finally analyzed 4987 questionnaires. Four hundred and eighty-seven participants indicated gluten-related symptoms "always" or "most of the time" (SR-NCGS subjects), while 121 already had a medical diagnosis of NCGS. The minimum prevalence figure of SR-NCGS is 6.4% (95%CI: 6.0-6.9), with a higher prevalence in females (79.9%). The most frequent gluten-related symptoms were bloating, abdominal pain and tiredness. CONCLUSIONS: The high prevalence of people reporting symptoms after gluten ingestion requires that the diagnosis of NCGS should be ascertained with a double-blind controlled study to limit the number of people who improperly approach a gluten-free diet.

Prebiotics in the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications.

Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit. Compared to probiotics there are few studies with prebiotics in children. Most studies have been performed using infant formula supplemented with prebiotics, while add-on prebiotic supplementation as prevention or treatment of childhood gastrointestinal disorders has rarely been reported. The aim of this position paper was to summarize evidence and make recommendations for prebiotic supplementation in children with gastrointestinal diseases. Recommendations made are based on publications up to January 1, 2023. Within the scope of the European Society for Paediatric Gastroenterology Hepatology and Nutrition Special Interest Group on Gut Microbiota and Modifications, as in our previous biotic recommendations, at least two randomized controlled clinical trials were required for recommendation. There are some studies showing benefits of prebiotics on selected outcomes; however, we cannot give any positive recommendations for supplementing prebiotics in children with gastrointestinal disorders.

Gastrointestinal involvement in STEC-associated hemolytic uremic syndrome: 10 years in a pediatric center.

BACKGROUND: The gastrointestinal (GI) tract represents one of the main targets of typical hemolytic uremic syndrome (HUS) in children. In this observational study, we tried to establish (1) the main features of GI complications during STEC-HUS and (2) the relationship between Escherichia coli serotypes and Shiga toxin (Stx) variants with hepatopancreatic involvement. METHODS: A total of 79 STEC-HUS patients were admitted to our pediatric nephrology department between January 2012 and June 2021. Evidence of intestinal, hepatobiliary, and pancreatic involvements was reported for each patient, alongside demographic, clinical, and laboratory features. Frequency of gastrointestinal complications across groups of patients infected by specific E. coli serotypes and Stx gene variants was evaluated. RESULTS: Six patients developed a bowel complication: two developed rectal prolapse, and four developed bowel perforation which resulted in death for three of them and in bowel stenosis in one patient. Acute pancreatitis was diagnosed in 13 patients. An isolated increase in pancreatic enzymes and/or liver transaminases was observed in 41 and 15 patients, respectively. Biliary sludge was detected in three, cholelithiasis in one. Forty-seven patients developed direct hyperbilirubinemia. Neither E. coli serotypes nor Shiga toxin variants correlated with hepatic or pancreatic involvement. CONCLUSIONS: During STEC-HUS, GI complications are common, ranging from self-limited elevation of laboratory markers to bowel perforation, a severe complication with a relevant impact on morbidity and mortality. Hepatopancreatic involvement is frequent, but usually short-lasting and self-limiting.

Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex.

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.

Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study.

Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose-type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

INTRODUCTION: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. METHODS: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). RESULTS: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. DISCUSSION: Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Twelve Months with COVID-19: What Gastroenterologists Need to Know.

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.

Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet.

BACKGROUND & AIMS: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Synaptic Mechanisms Underlying the Network State-Dependent Recruitment of VIP-Expressing Interneurons in the CA1 Hippocampus.

Disinhibition is a widespread circuit mechanism for information selection and transfer. In the hippocampus, disinhibition of principal cells is provided by the interneuron-specific interneurons that express the vasoactive intestinal polypeptide (VIP-IS) and innervate selectively inhibitory interneurons. By combining optophysiological experiments with computational models, we determined the impact of synaptic inputs onto the network state-dependent recruitment of VIP-IS cells. We found that VIP-IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, by integrating their intrinsic and synaptic properties into computational models, we predicted recruitment of these cells between the rising phase and peak of theta oscillation and during ripples. Two-photon Ca2+-imaging in awake mice supported in part the theoretical predictions, revealing a significant speed modulation of VIP-IS cells and their preferential albeit delayed recruitment during theta-run epochs, with estimated firing at the rising phase and peak of the theta cycle. However, it also uncovered that VIP-IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of VIP-IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.

Limosilactobacillus reuteri Strains as Adjuvants in the Management of Helicobacter pylori Infection.

Helicobacter pylori (HP) is a Gram-negative bacterium which finds its suitable habitat in the stomach. The infection affects about half of the global population with high variability in prevalence among regions and for age. HP is the main causative agent of chronic active gastritis, peptic and duodenal ulcers, and may be the primary cause of gastric cancer or MALT lymphoma. Due to the high rate of failure of eradication therapy in various countries and the increase in antibiotic resistance reported in the literature, there is an ever wider need to seek alternative therapeutic treatments. Probiotics seem to be a promising solution. In particular, the Limosilactobacillus reuteri (L. reuteri) species is a Gram-positive bacterium and is commonly found in the microbiota of mammals. L. reuteri is able to survive the gastric acid environment and bile and to colonize the gastric mucosa. This species is able to inhibit the growth of several pathogenic bacteria through different mechanisms, keeping the homeostasis of the microbiota. In particular, it is able to secrete reuterin and reutericycline, substances that exhibit antimicrobial properties, among other molecules. Through the secretion of these and the formation of the biofilm, it has been found to strongly inhibit the growth of HP and, at higher concentrations, to kill it. Moreover, it reduces the expression of HP virulence factors. In clinical trials, L. reuteri has been shown to decrease HP load when used as a single treatment, but has not achieved statistical significance in curing infected patients. As an adjuvant of standard regimens with antibiotics and pump inhibitors, L. reuteri can be used not only to improve cure rates, but especially to decrease gastrointestinal symptoms, which are a common cause of lack of compliance and interruption of therapy, leading to new antibiotic resistance.

Input-Specific Synaptic Location and Function of the α5 GABAA Receptor Subunit in the Mouse CA1 Hippocampal Neurons.

Hippocampus-dependent learning processes are coordinated via a large diversity of GABAergic inhibitory mechanisms. The α5 subunit-containing GABAA receptor (α5-GABAAR) is abundantly expressed in the hippocampus populating primarily the extrasynaptic domain of CA1 pyramidal cells, where it mediates tonic inhibitory conductance and may cause functional deficits in synaptic plasticity and hippocampus-dependent memory. However, little is known about synaptic expression of the α5-GABAAR and, accordingly, its location site-specific function. We examined the cell- and synapse-specific distribution of the α5-GABAAR in the CA1 stratum oriens/alveus (O/A) using a combination of immunohistochemistry, whole-cell patch-clamp recordings and optogenetic stimulation in hippocampal slices obtained from mice of either sex. In addition, the input-specific role of the α5-GABAAR in spatial learning and anxiety-related behavior was studied using behavioral testing and chemogenetic manipulations. We demonstrate that α5-GABAAR is preferentially targeted to the inhibitory synapses made by the vasoactive intestinal peptide (VIP)- and calretinin-positive terminals onto dendrites of somatostatin-expressing interneurons. In contrast, synapses made by the parvalbumin-positive inhibitory inputs to O/A interneurons showed no or little α5-GABAAR. Inhibiting the α5-GABAAR in control mice in vivo improved spatial learning but also induced anxiety-like behavior. Inhibiting the α5-GABAAR in mice with inactivated CA1 VIP input could still improve spatial learning and was not associated with anxiety. Together, these data indicate that the α5-GABAAR-mediated phasic inhibition via VIP input to interneurons plays a predominant role in the regulation of anxiety while the α5-GABAAR tonic inhibition via this subunit may control spatial learning.SIGNIFICANCE STATEMENT The α5-GABAAR subunit exhibits high expression in the hippocampus, and regulates the induction of synaptic plasticity and the hippocampus-dependent mnemonic processes. In CA1 principal cells, this subunit occupies mostly extrasynaptic sites and mediates tonic inhibition. Here, we provide evidence that, in CA1 somatostatin-expressing interneurons, the α5-GABAAR subunit is targeted to synapses formed by the VIP- and calretinin-expressing inputs, and plays a specific role in the regulation of anxiety-like behavior.

Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

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 symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.

Preventing and Treating Colic.

Colic is a common and distressing functional gastrointestinal disorder during infancy. It is a behavioral phenomenon in infants aged 1-4 months involving prolonged inconsolable crying and agitated status with multifactorial etiology. Colic can be considered as a benign, self-limited process because the baby normally grows and feeds even with transient irritable mood. Nevertheless, infantile colic is a common difficulty causing anxiety during parenthood and a recurrent reason for them to seek medical help, especially if it is the first child. The causes of colic can be classified as non-gastrointestinal or gastrointestinal. The former includes altered feeding techniques, modified child-parent relationship, immaturity of central nervous system, behavioral etiology, and maternal smoking or nicotine replacement therapy. Instead, the latter involves inadequate production of lactase enzyme, cow's milk protein intolerance, alteration of intestinal microbiota, gastrointestinal immaturity, or inflammation which causes intestinal hyperperistalsis due to increase in serotonin secretion and motilin receptor expression.Probiotics may play a crucial part in the manipulation of the microbiota. Probiotic administration is likely to maintain intestinal homeostasis through the modulation of permeability and peristalsis, influencing the gut-brain axis and inhibiting hypersensitivity. This is a decisive field in the development of preventive and therapeutic strategies for infantile colic. However, further studies are needed for each specific formulation in order to better characterize pharmacodynamic and pharmacokinetic properties and to evaluate their application as a possible preventive strategy if administered early during infancy against the later development of pain-related FGIDs.

Safety of Oats in Children with Celiac Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the long-term validity and safety of pure oats in the treatment of children with celiac disease. STUDY DESIGN: This noninferiority clinical trial used a double-blind, placebo-controlled, crossover design extended over 15 months. Three hundred six children with a biopsy-proven diagnosis of celiac disease on a gluten-free diet for ≥2 years were randomly assigned to eat specifically prepared gluten-free food containing an age-dependent amount (15-40 g) of either placebo or purified nonreactive varieties of oats for 2 consecutive 6-month periods separated by washout standard gluten-free diet for 3 months. Clinical (body mass index, Gastrointestinal Symptoms Rating Scale score), serologic (IgA antitransglutaminase antibodies, and IgA anti-avenin antibodies), and intestinal permeability data were measured at baseline, and after 6, 9, and 15 months. Direct treatment effect was evaluated by a nonparametric approach using medians (95% CI) as summary statistic. RESULTS: After the exclusion of 129 patients who dropped out, the cohort included 177 children (79 in the oats-placebo and 98 in the placebo-oats group; median, 0.004; 95% CI, -0.0002 to 0.0089). Direct treatment effect was not statistically significant for clinical, serologic, and intestinal permeability variables (body mass index: median, -0.5; 95% CI, -0.12 to 0.00; Gastrointestinal Symptoms Rating Scale score: median, 0; 95% CI, -2.5 to 0.00; IgA antitransglutaminase antibodies: median, -0.02; 95% CI, -0.25 to 0.23; IgA anti-avenin antibodies: median, -0.0002; 95% CI, -0.0007 to 0.0003; intestinal permeability test: median, 0.004; 95% CI, -0.0002 to 0.0089). CONCLUSIONS: Pure nonreactive oat products are a safe dietary choice in the treatment of children with celiac disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00808301.

Intervention for Dysbiosis in Children Born by C-Section.

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.

Introduction of gluten, HLA status, and the risk of celiac disease in children.

BACKGROUND: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS: Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).

Selected Probiotic Lactobacilli Have the Capacity To Hydrolyze Gluten Peptides during Simulated Gastrointestinal Digestion.

The aim of this study was to demonstrate the capacity of probiotic lactobacilli to hydrolyze immunogenic gluten peptides. Eighteen commercial strains of probiotic lactobacilli with highly variable peptidase activity (i.e., aminopeptidase N, iminopeptidase, prolyl endopeptidyl peptidase, tripeptidase, prolidase, prolinase, and dipeptidase), including toward Pro-rich peptides, were tested in this study. Ten probiotic strains were selected on the basis of their specific enzyme activity. When pooled, these 10 strains provided the peptidase portfolio that is required to completely degrade the immunogenic gluten peptides involved in celiac disease (CD). The selected probiotic mixture was able to completely hydrolyze well-known immunogenic epitopes, including the gliadin 33-mer peptide, the peptide spanning residues 57 to 68 of the α9-gliadin (α9-gliadin peptide 57-68), A-gliadin peptide 62-75, and γ-gliadin peptide 62-75. During digestion under simulated gastrointestinal conditions, the pool of 10 selected probiotic lactobacilli strongly hydrolyzed the wheat bread gluten (ca. 18,000 ppm) to less than 10 ppm after 360 min of treatment. As determined by multidimensional chromatography (MDLC) coupled to nanoelectrospray ionization (nano-ESI)-tandem mass spectrometry (MS/MS), no known immunogenic peptides were detected in wheat bread that was digested in the presence of the probiotics. Accordingly, the level of cytokines (interleukin 2 [IL-2], IL-10, and interferon gamma [IFN-γ]) produced by duodenal biopsy specimens from CD patients who consumed wheat bread digested by probiotics was similar to the baseline value (negative control). Probiotics that specifically hydrolyze gluten polypeptides could also be used to hydrolyze immunogenic peptides that contaminate gluten-free products. This could provide a new and safe adjunctive therapy alternative to the gluten-free diet (GFD).IMPORTANCE This study confirmed that probiotic Lactobacillus strains have different enzymatic abilities for hydrolyzing polypeptides, including the Pro-rich epitopes involved in the pathology of CD. Ten lactobacilli with complementary peptidase activities that hydrolyze gluten peptides during simulated gastrointestinal digestion were selected and tested. The results collected showed the potential of probiotic formulas as novel dietary treatments for CD patients.

Mode of Delivery and Risk of Celiac Disease: Risk of Celiac Disease and Age at Gluten Introduction Cohort Study.

OBJECTIVE: To determine whether the mode of delivery is associated with the risk of celiac disease (CD) in a cohort of children genetically predisposed to CD prospectively followed from birth. STUDY DESIGN: By telephone interview, we recorded information on the mode of delivery of children participating in the Risk of Celiac Disease and Age at Gluten Introduction study, a multicenter, prospective intervention trial that compared early and delayed introduction of gluten in infants with at least 1 first-degree relative affected with CD. The human leukocyte antigen genotype was determined at 15 months of age, and serologic screening for CD was performed at 15, 24, and 36 months of age and at 5, 8, and 10 years of age. Patients with positive serologic findings underwent intestinal biopsy. The primary outcome of the current study was the prevalence of CD autoimmunity and overt CD at 5 years of age, according to the mode of delivery. RESULTS: The study-group included 553 children at CD risk because of positivity for human leukocyte antigen-DQ2, -DQ8, or both. We obtained data on the mode of delivery from 431 of 553 children; 233 of 431 children were born by vaginal delivery (54%). At 5 years of age, the prevalence of CD autoimmunity or overt CD was not different between children born by cesarean or vaginal delivery (24% and 19%, P = .2; 19% and 14%, P = .2 respectively, by the log-rank test). CONCLUSIONS: In this cohort of children genetically predisposed to CD, the mode of delivery did not influence the risk of developing CD.

Indications and Recommendations by Societies and Institutions for the Use of Probiotics and Prebiotics in Paediatric Functional Intestinal Disorders.

PURPOSE OF REVIEW: To report the indications and/or recommendations by Societies and Institutions for the use of probiotics and prebiotics in functional intestinal disorders in childhood. RECENT FINDINGS: 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. SUMMARY: 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.