NOD2 and inflammation: current insights

The nucleotide-binding oligomerization domain (NOD) protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene

Gelatin tannate for acute childhood gastroenteritis: a randomized, single-blind controlled trial

Background Oral rehydration therapy is the recommended treatment for acute childhood gastroenteritis. The aim of this study was to assess the efficacy and safety of gelatin tannate plus oral rehydration compared with oral rehydration alone. Methods We conducted a multicenter, parallel, randomized, controlled, single-blind, prospective, open-label trial. A central randomization center used computer generated tables to allocate treatments. The study was performed in two medical centers in Italy. Sixty patients 3–72 months of age with acute gastroenteritis were recruited (median age 18 months; age range 3–66 months): 29 received an oral rehydration solution (ORS) and 31 an ORS plus gelatin tannate (ORS ? G). The primary outcome was the number of bowel movements 48 and 72 h after initiating treatment. Secondary outcomes were: duration of diarrhea, stool characteristics and adverse events. Results No patient was lost at follow-up. No significant difference in the number of bowel movements after 48 h was reported (2.7 ± 1.3 ORS ? G; 3.2 ± 0.8 ORS; p = 0.06), although the ORS ? G group showed a significant improvement in stool consistency (3.7 ± 1.0 vs. 4.3 ± 0.8; p = 0.005). At 72 h, a significant reduction in bowel movements was reported in the ORS ? G group compared with the ORS group (1.0 ± 1.4 vs. 2.0 ± 1.7; p = 0.01). Mean duration of diarrhea was significantly lower in the ORS ? G group than in the ORS only group (76.8 ± 19.2 vs. 108 ± 24.0 h; p.0001). No adverse events were reported. Conclusions Gelatin tannate added to oral rehydration in children with acute diarrhea was associated with a significant decrease in bowel movements at 72 h, with an early improvement in the stool consistency and shorter disease duration

Capsule endoscopy in pediatrics: a 10-years journey.

Video capsule endoscopy (CE) for evaluation the esophagus (ECE), small bowel (SBCE) and the colon (CCE) is particularly useful in pediatrics, because this imaging modality does not require ionizing radiation, deep sedation or general anesthesia. The risk of capsule retention appears to be dependent on indication rather than age and parallels the adult experience by indication, making SBCE a relatively safe procedure with a significant diagnostic yield. The newest indication, assessment of mucosal change, greatly enhances and expands its potential benefit. The diagnostic role of CE extends beyond the SB. The use of ECE also may enhance our knowledge of esophageal disease and assist patient care. Colon CCE is a novel minimally invasive and painless endoscopic technique allowing exploration of the colon without need for sedation, rectal intubation and gas insufflation. The limited data on ECE and CCE in pediatrics does not yet allow the same conclusions regarding efficacy; however, both appear to provide safe methods to assess and monitor mucosal change in their respective areas with little discomfort. Moreover, although experience has been limited, the patency capsule may help lessen the potential of capsule retention; and newly researched protocols for bowel cleaning may further enhance CE's diagnostic yield. However, further research is needed to optimize the use of the various CE procedures in pediatric populations

Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study.

AIM: To assess the value of long-chain omega-3 fatty acids (FAs) supplementation in addition to amino-salicylic-acid (5-ASA) in pediatric patients with Crohn's disease (CD). METHODS: Thirty-eight patients (20 males and 18 females, mean age 10.13 years, range 5-16 years) with CD in remission were randomized into two groups and treated for 12 mo. Group I (18 patients) received 5-ASA (50 mg/kg/d)+ omega-3 FAs as triglycerides in gastro-resistant capsules, 3 g/d (eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g). Group II (20 patients) received 5-ASA (50 mg/kg/d)+ olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS: The number of patients who relapsed at 1 year was significantly lower in group I than in group II (P < 0.001). Patients in group I had a significant increase in the incorporation of EPA and DHA (P < 0.001) and a decrease in the presence of arachidonic acids. CONCLUSION: Enteric-coated omega-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD

Emerging roles of gut virome in pediatric diseases

In the last decade, the widespread application of shotgun metagenomics provided extensive characterization of the bacterial “dark matter” of the gut microbiome, propelling the development of dedicated, standardized bioinformatic pipelines and the systematic collection of metagenomic data into comprehensive databases. The advent of next-generation sequencing also unravels a previously underestimated viral population (virome) present in the human gut. Despite extensive efforts to characterize the human gut virome, to date, little is known about the childhood gut virome. However, alterations of the gut virome in children have been linked to pathological conditions such as inflammatory bowel disease, type 1 diabetes, malnutrition, diarrhea and celiac diseas

Effects of omeprazole on mechanisms of gastroesophageal reflux in childhood

Prolonged recordings of esophageal motility have shown that dynamic changes of lower esophageal sphincter (LES) pressure such as transient LES relaxation and LES pressure drifts are the most common mechanisms underlying gastroesophageal reflux (GER). The coexistence of a delayed gastric emptying has also been reported in a high proportion of patients with reflux disease. However, not much information is available on the effects of antireflux therapy on the pathogenetic mechanisms of GER. The purpose of this study was to determine in a group of children with severe reflux disease the effect of omeprazole therapy on motor changes of LES underlying GER as well as on gastric emptying time. Twenty-two children (median age: 6.6 years) with GER disease, refractory to combined ranitidine and cisapride administration, entered into an eight-week omeprazole course. Ten subjects with moderate GER disease served as controls (median age: 6.0 years). Before and after omeprazole administration, the following variables were assessed: esophagitis grading, fasting and fed simultaneous prolonged recording of distal esophageal sphincter pressure (with a sleeve catheter) and intraesophageal pH, LES and esophageal peristalsis amplitude, and gastric emptying time of a mixed solid-liquid meal (measured with gastric ultrasound). As compared to controls, patients showed a higher rate of transient LES relaxation and LES pressure drift (P < 0.01), a reduced amplitude of basal sphincter pressure (P < 0.01) and peristalsis (P < 0.05), and a more prolonged gastric emptying time (P < 0.05). After ending omeprazole, there was no significant change in any of the motor abnormalities of the esophagus and in gastric emptying time despite a marked improvement of symptoms and esophagitis in all patients. Sixteen patients were symptomatic when reevaluated on a clinical basis two months after ending therapy. We conclude that in children with severe GER disease, an abnormally high rate of both transient LES relaxation and LES pressure drift and slow gastric emptying are not affected by omperazole treatment, even though esophageal mucosal damage is markedly improved or cured. These abnormalities represent a primary motor disorder and can be implicated in the refractoriness of reflux disease

Fecal and mucosal microbiota profiling in pediatric inflammatory bowel diseases

An altered gut microbiota profile has been widely documented in inflammatory bowel diseases (IBD). The intestinal microbial community has been more frequently investigated in the stools than at the level of the mucosa, while most of the studies have been performed in adults. We aimed to define the gut microbiota profile either by assessing fecal and colonic mucosa samples (inflamed or not) from pediatric IBD patients

Screening for type 1 diabetes-, thyroid-, gastric-, and adrenal-specific humoral autoimmunity in 529 children and adolescents with celiac disease at diagnosis identifies as positive one in every nine patients

No abstract availabl