Use of Limosilactobacillus reuteri DSM 17938 in paediatric gastrointestinal disorders: an updated review.

Strains of lactobacilli are the most widely used probiotics and can be found in a large variety of food products and food supplements throughout the world. In this study, the evidence on Limosilactobacillus reuteri DSM 17938 (LR DSM 17938) has been reviewed. This species secretes reuterin and other substances singularly or in microvesicles, inhibiting pathogen growth and interacting with the intestinal microbiota and mucosa, restoring homeostasis. The use of LR DSM 17938 has been exploited in several pathological conditions. Preclinical research has shown that this probiotic can ameliorate dysbiosis and, by interacting with intestinal mucosal cells, can raise the pain threshold and promote gastrointestinal motility. These aspects are amongst the significant components in functional gastrointestinal disorders, such as colic and regurgitation in infants, functional abdominal pain and functional constipation in children and adolescents. This strain can decrease the duration of acute diarrhoea and hospitalization for acute gastroenteritis but does not seem to prevent nosocomial diarrhoea and antibiotic-associated diarrhoea. Because of its ability to survive in the gastric environment, it has been tested in Helicobacter pylori infection, showing a significant decrease of antibiotic-associated side effects and a tendency to increase the eradication rate. Finally, all these studies have shown the excellent safety of LR DSM 17938 even at higher dosages. In conclusion data from various clinical trials here reviewed can guide the clinician to find the correct dose, frequency of administration, and therapy duration.

Randomized Double-Blind Placebo-Controlled Crossover Trial for the Diagnosis of Non-Celiac Gluten Sensitivity in Children.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 in >60% of cases. The registration identifier in ClinicalsTrials.gov is NCT02431585.

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.

A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.

BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

The overweight: a rare presentation of celiac disease.

We describe the nutritional status of a cohort of celiac disease (CD) children at presentation and during follow-up on gluten-free diet (GFD). Two Italian centers (Rome and Bari) prospectively enrolled 445 biopsy-confirmed CD children, diagnosed between 2009 and 2013. Body Mass Index was used as a measure of nutritional status according to Italian growth charts of Cacciari. The overweight/obese subject was 7.8% at onset and did not significantly increase during follow-up (9.8% at final assessment). The prevalence of overweight/obesity was significantly higher among males than females. Furthermore, overweight/obesity children as compared with those with normal weight were significantly older and had significantly lower levels of tTG antibodies. This study shows that some CD children are obese/overweight at diagnosis; therefore, overweight/obesity can be considered a rare but a possible mode of CD presentation. Thus, CD diagnosis must be considered even in overweight/obese children where this diagnosis can be easily missed.

Prevention of functional gastrointestinal disorders in neonates: clinical and socioeconomic impact.

Infantile colic, gastro-oesophageal reflux and constipation are the most common functional gastrointestinal disorders (FGIDs) affecting infants during the first months of life. Despite infantile colic, functional constipation and regurgitation had a self-limited pattern, they are considered a risk factor for developing different disorders later in life. The pathophysiology of these functional diseases is still controversial but there is growing evidence that an abnormal gut microbiota colonisation may play a crucial role. An early probiotic supplementation could determine a change in colonisation and may represent a new strategy for preventing FGIDs.

Treatment of celiac disease: from gluten-free diet to novel therapies.

Gluten-free diet (GFD) is the cornerstone treatment for celiac disease (CD). This diet excludes the protein gluten a protein forum in in grains such as wheat, barley, rye and triticale. Gluten causes small intestines inflammation in patients with CD and eating a GFD helps these patients in controlling signs and symptoms and prevent complications. Following a GFD may be frustrating, however, it is important to know that plenty of foods are naturally gluten-free and nowadays is relatively easy to find substitutes for gluten-containing foods. Certain grains, such as oats, are generally safe but can be contaminated with wheat during growing and processing stages of production. For this reason, it is generally recommended avoiding oats unless they are specifically labelled gluten-free. Other products that may contain gluten include food additives, such as malt flavouring, modified food starch and some supplement and/or vitamins that use gluten as a binding agent. Cross-contamination occurs when gluten-free foods come into contact with foods that contain gluten. It can happen during the manufacturing process or if the same equipment is used to make a variety of products. Cross-contamination can also occur at home if foods are prepared on common surfaces or with utensils that have not been cleaned after being used to prepare gluten-containing foods (using a toaster for gluten-free and regular bread). Although safe and effective, the GFD is not ideal: it is expensive, of limited nutritional value, and not readily available in many countries. Consequently, a need exists for novel, non-dietary therapies for celiac disease. Advances in understanding the immunopathogenesis of CD have suggested several types of therapeutic strategies alternative to the GFD. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to CD-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that re-establish mucosal homeostasis and tolerance to gluten antigens are also being explored.

Subclinic cardiac involvement in paediatric patients with celiac disease: a novel sign for a case finding approach.

The aim of the present work was to assess the prevalence of early cardiac involvement in children with celiac disease (CD), and the impact of a gluten free diet (GFD) on this issue. Sixty CD children was compared with a control group of 45 healthy children by an echocardiographic examination. CD patients were re-evaluated 1-year after 1-year GFD. Main outcome measures were ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVSD), any regurgitating valve lesions. Mild cardiac involvement was found in 13 CD children and in one control (21.7% vs. 2.2%; p=0.003), and was secondary to regurgitation of mitral valve, aortic valve, pulmonary and tricuspid valve, or to impaired ejection fraction. CD children as compared to controls had significantly lower contractility indices, and higher left ventricular dimensions. In patients adhering to the GFD all valve regurgitations resolved, and the echocardiographic parameters significantly improved. Subclinical cardiac involvement in CD children is quite frequent, and GFD may exert a beneficial effect on the overall cardiac performance.

Probiotics and Helicobacter pylori infection in children.

Approximately 50 percent of the world population is infected with Helicobacter pylori (H. pylori), with the highest prevalence rates in developing countries. The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30 percent. Current interest in probiotics as therapeutic agents against Helicobacter pylori is stimulated by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Available data in children indicate that probiotics seem to be efficacious for the prevention of antibiotic associated side-effects, and might be of help for the prevention of Helicobacter pylori complications by decreasing Helicobacter pylori density and gastritis, and for the prevention of Helicobacter pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the Helicobacter pylori eradication rate.

Randomised clinical trial: Lactobacillus reuteri DSM 17938 vs. placebo in children with acute diarrhoea--a double-blind study.

BACKGROUND: Probiotics may be of help for the management of acute diarrhoea, however, the effect is strain specific and efficacy needs to be proven. AIM: To test the efficacy and safety of Lactobacillus reuteri DSM 17938 derived from L. reuteri ATCC 55730 in children with acute diarrhoea. Primary outcomes were the rate of unresolved diarrhoea after 3 days of treatment and duration of diarrhoea. METHODS: Children (6-36 months), hospitalised in three paediatric hospitals in Southern Italy for acute diarrhoea with clinical signs of dehydration were randomised to receive in a double-blind fashion either L. reuteri (dose of 4 × 10(8) colony-forming units/die) or placebo. RESULTS: Out of 96 eligible children, 74 were enrolled, five patients were withdrawn; 35 in the L. reuteri group and 34 in the placebo group. Lactobacillus reuteri significantly reduced the duration of watery diarrhoea as compared with placebo (2.1 ± 1.7 days vs. 3.3 ± 2.1 days; P < 0.03); on day two and three of treatment watery diarrhoea persisted in 82% and 74% of the placebo and 55% and 45% of the L. reuteri recipients respectively (P < 0.01; P < 0.03). Finally, children receiving L. reuteri had a significantly lower relapse rate of diarrhoea (15% vs. 42%; P < 0.03). There was not a significant difference in hospital stay between the groups. No adverse events were recorded. CONCLUSION: Our study shows that L . reuteri DSM 17938 as an adjunct to rehydration therapy is efficacious in the treatment of acute diarrhoea reducing the frequency, duration and recrudescence rate of the disease.

Recurrent peptic ulcer disease in a pediatric patient with type 1 neurofibromatosis and primary ciliary dyskinesia.

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal complications are rare, especially during childhood. In adults, only two cases of peptic ulcer have been reported in neurofibromatosis, both due to Zollinger-Ellison syndrome. Peptic ulcer disease (PUD) may be primary or secondary in nature and it may be life threatening in the acute phase due to the risk of perforation. A case of recurrent gastrointestinal hemorrhage in a child with systemic neurofibromatosis and primary ciliary dyskinesia (PCD) is presented. The upper gastrointestinal endoscopy revealed the presence of multiple gastric ulcers. The ulcers scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after the suspension. Laboratory and imaging studies excluded Zollinger-Ellison syndrome and other known causes of PUD, suggesting a potential role of neurofibromatosis itself and primary ciliary dyskinesia in developing of recurrent PUD. As early diagnosis of PUD is vital for patient survival, this case report highlights the possible association of neurofibromatosis and PCD with this condition, responsive to PPI therapy and the potential need of gastric protection before complications arise.

Effects of probiotic and prebiotic on gastrointestinal motility in newborns.

To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk. The aim of this study was to evaluate the effects of prebiotic, probiotic added to a standard formula on gastrointestinal motility respect to placebo-formula. Cutaneous electrogastrography (EGG) and ultrasound gastric emptying (GE) were performed in 49 preterm newborns. 17 newborns were exclusively breast-fed; 32 were randomly assigned to receive prebiotic-added formula (0.8 g/dl of a mixture from scGOS and lcFOS, ratio 9:1) (10), a probiotic-added formula (L. reuteri at dose of 1x10(8) colony forming units (CFU) per day) (10), a formula with placebo (12) for 30 days. No difference was seen in the nutritional parameters and no adverse events were reported. After the intervention period, the prebiotic, probiotic, and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group (ANOVAon ranks p<0.001; Dunn test vs control: prebiotic, probiotic and breast-milk vs placebo formula p<0.05; and ANOVA on ranks p=0.005; Dunn test vs control: prebiotic, probiotic and breast-milk vs placebo formula p<0.05, respectively). Feeding preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk.

[Primary allergy prevention: partially or extensively hydrolyzed infant formulas?]. / Prevenzione dietetica primaria dell'allergia: idrolisati parziali o estensivi?

The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. In infants from ''high-risk'' families (i.e. those with one or two parents and/or a sibling with food allergy, eczema, asthma or allergic rhinitis) food allergen avoidance has been advocated as means of preventing the development of atopic disease. The aim of this review was to evaluate the allergy preventive potential of partially or extensively hydrolyzed formulas. When breast-feeding is not possible or supplemental feeding is needed, infants from atopic families should be given a hydrolyzed infant formula for the first 6 month of life. High-risk infants without a history of eczema in a primary relative will receive the protective effect from the less expensive partial hydrolyzed formula (p-HF); whereas those infants who have first-degree relatives with eczema should receive the extensively hydrolyzed formula (e-HF).

[Phytoterapy: a glimmer of hope in the prevention of recurrent respiratory tract infections in children]. / Fitoterapia: un barlume di speranza per la prevenzione delle infezioni respiratorie ricorrenti nel bambino.

Evidence on the efficacy of standardised phytoterapic extracts for the prevention of recurrent respiratory tract infections (RRTIs) in children is reviewed. Echinacea extracts are widely used in European countries and in the United States as immune-stimulating agents. However, further prospective, appropriately powered clinical studies are required to confirm their benefits in reducing duration and severity of RRTIs.

Multichannel intraluminal impedance to detect relationship between gastroesophageal reflux and apnoea of prematurity.

BACKGROUND: The association between gastroesophageal reflux and apnoea of prematurity is still controversial. Available data are biased by the heterogeneity of the infants enrolled as regard to some confounding factors and by the use of the traditional pH monitoring that is unable to detect non acid reflux events which might be prevalent in infants receiving frequent milk feeding. Multichannel intraluminal impedance has been recently introduced as a pH-independent method to investigate the bolus transport in hollow organs. OBJECTIVE: To assess if combined multichannel intraluminal impedance-pH study could be useful to detect an association between gastroesophageal reflux and apnoea of prematurity. METHODS: We prospectively evaluated a group of premature infants with apnoea of prematurity in absence of any confounding factors (ventilatory support, treatment with caffeine, permanent nasogastric tube, post-natal age older than 30 days) by simultaneous recording of 24-h multichannel intraluminal impedance-pH and cardiorespiratory monitoring. A temporal relationship between an apnoea and a reflux event was considered if both commenced within 20s of each other. RESULTS: Six premature infants [three male; median gestational age 31 weeks (range 27-36); birth weight 1335g (range 1200-2350); age at study 17 days (range 7-28)] were studied. A total of 405 reflux events [306 (76%) weakly acid and 99 acid reflux] and 142 apnoeas were detected. The frequency of apnoeas occurring during the reflux events period was significantly greater than the one calculated for reflux-free period [0.42/min (0.00-1.28) versus 0.016/min (0.003-0.028); p<0.05]. The sub-analysis based on chemical composition and duration of refluxate showed that the frequency of apnoeas associated with weakly acid reflux events was significantly greater than the one calculated for reflux-free period [0.416/min (0.00-1.30) versus 0.016/min (0.003-0.028), respectively; p<0.05] and that the frequency of apnoeas occurring during reflux events longer than 30s was significantly higher than those occurring during shorter reflux events (22% versus 11%; p<0.004). CONCLUSION: Our data show that weakly acidic reflux events are more prevalent than acid reflux events in premature infants, confirming the need for the use of multichannel intraluminal impedance-pH monitoring for diagnosis of gastroesophageal reflux in those patients. Gastroesophageal reflux and apnoea of prematurity are both common occurrences and, in our experience, may be temporally related especially as regard to weakly acid refluxate and reflux events longer than 30s.

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy.

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment.

Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomized placebo controlled trial.

BACKGROUND: Helicobacter pylori eradication fails in about 25-30% of children, particularly because of the occurrence of resistance to antibiotics and side-effects. AIM: To determine whether adding the Lactobacillus reuteri to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden in children. METHODS: Forty H. pylori-positive children (21 males; median age: 12.3 years) were consecutively treated with 10-day sequential therapy [omeprazole + amoxycillin for 5 days, and omeprazole + clarithromycin + tinidazole for other 5 days] and blindly randomized to receive either L. reuteri ATCC 55730 (10(8) CFU) or placebo. All children completed the Gastrointestinal Symptom Rating Scale (GSRS) at entry, during and after treatment. H. pylori status was assessed after 8 weeks by (13)C-urea breath test. RESULTS: Overall, in all probiotic supplemented children when compared with those receiving placebo there was a significant reduction of GSRS score during eradication therapy (4.1 +/- 2 vs. 6.2 +/- 3; P < 0.01) and at the end of follow-up (3.2 +/- 2 vs. 5.8 +/- 3.4; P < 0.009). Overall, children receiving L. reuteri report less symptoms than those receiving placebo. CONCLUSION: L. reuteri is capable of reducing frequency and intensity of antibiotic-associated side-effects during eradication therapy for H. pylori.