Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.

BACKGROUND AND AIMS: Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known. METHODS: We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]. RESULTS: In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum. CONCLUSIONS: Nod2 protects the gut from colitis spreading to small intestine.

HLA-DQ Genotyping, Duodenal Histology, and Response to Exclusion Diet in Autistic Children With Gastrointestinal Symptoms.

OBJECTIVES: A correlation between autism spectrum disorders (ASDs) and gastrointestinal (GI) problems, and a possible link between gluten consumption and ASD have been increasingly reported. Gluten/casein-free diet (GCFD) is often undertaken, with conflicting results. This study aimed at evaluating the distribution of human leukocyte antigen (HLA)-DQ2/DQ8 typing among patients with ASD with GI symptoms, together with its correlation with duodenal histology and response to GCFD. METHODS: Between 2002 and 2015 all patients with ASD with GI symptoms referred to our outpatient clinic, displaying clinical, laboratory, or ultrasound findings suggestive of organic disease, underwent endoscopy, celiac disease (CD) serum antibodies testing and HLA-DQ2/DQ8 genotyping. Patients were prescribed a 6-month GCFD, and then clinically reassessed. RESULTS: Among 151 enrolled patients, 134 (89%) were negative for CD-specific antibodies; 72 (48%) were positive for HLA-DQ2/DQ8; and 56 (37%) showed duodenal microscopic inflammation. Clinical improvement was observed in non-CD patients irrespective of the rigorous or partial adherence to the diet, being the difference nonstatistically significant. Response to diet was related to the presence of histological duodenal alterations at baseline (odds ratio 11.323, 95% confidence interval 1.386-92.549 for Marsh 2 pattern), but not to HLA-DQ2/DQ8 positivity (odds ratio 1.120, 95% confidence interval 0.462-2.716). CONCLUSIONS: Our data suggest that children with ASD with GI symptoms have a high prevalence of duodenal intraepithelial lymphocytic infiltration, which seems to be linked to a mechanism other than autoimmune response to gluten consumption. Alteration of duodenal histology, but not the HLA-DQ2/DQ8 status, was associated with clinical response to the diet.

Duodenal mucosa FOXP3 expression in different etiologies of lymphocytic duodenosis.

BACKGROUND/AIMS: In celiac disease there is an increase of lymphocytes expressing FOXP3 in the intestinal mucosa associated with varying degrees of villous atrophy. Our aim was to evaluate FOXP3 expression in duodenal mucosa with lymphocytic enteritis according to aetiology and correlation with lymphocytes T-γδ. METHODS: We compared three adult patient groups suffering lymphocytic enteritis: celiacs following a gluten-free diet (n=12), first-degree relatives of celiac patients with genetic risks (n=14) and patients with functional dyspepsia (n=14), along with a control group not suffering from duodenal enteritis (n=16). The population of duodenal lymphocytes was analysed by immunohistochemistry assays for CD3+ characterisation and FOXP3 expression. Quantification of lymphocytes T-γδ in duodenal mucosa was performed by flow cytometry in fresh tissue samples. RESULTS: Presence of lymphocytes T-γδ was significantly higher in the group of celiac individuals compared to the group of relatives of these individuals (37.44 vs 5,52: p<0.0001) and the group with functional dyspepsia (37.44 vs 11.76: p=0.008). FOXP3 expression was also significantly higher in the celiac group than in the groups of relatives (18.85 vs 6.31; p=0.001) and functional dyspepsia patients (18.85 vs 7.61; p=0.023). The proportion of lymphocytes T-γδ and FOXP3- expressing lymphocytes was similar in the control group to that in the relatives or functional dyspepsia groups. CONCLUSIONS: Lymphocytic enteritis associated to celiac disease shows an increase of FOXP3 expression and lymphocytes T-γδ that is not detected in other etiologies of enteritis.

[The microbiocenosis of upper parts of digestive tract of children with gastroesophageal reflux disease and chronic gastroduodenitis].

The article considers the microbe specter of mucous coat of esophagus and stomach in children with gastro esophageal reflux disease and chronic gastroduodenitis. In patients with diseases of upper parts of digestive tract, the opportunistic pathogenic bacteria are isolated more often and their strains have aggression factors and cytotoxicity. In children with reflux disease the microbe landscape of esophagus is larger both in numerical and specific respect as compared to healthy adolescents and children with isolated gastroduodenitis.

[Colonic microenvironment in familial helicobacter infection]. / Mikroékologiia tolstoi kishki pri semeinom khelikobakterioze.

To elucidate the significance of the familial microenvironment in the genesis of Helicobacter infection, a clinical and instrumental investigation was made of 13 families selected by the probands who had digestive diseases associated with H. pylori: gastroduodenitis and duodenal ulcer disease. The occurrence of Helicobacter infection and gastritis in the family members was ascertained to be largely determined by their concurrent residence in the limited area, i.e. by the way of life. The contribution of the "family" factor in antral gastritis, fundal gastritis, and H. pylori infection was 60.0, 40.0, and about 90.0%, respectively. The patients with gastroenterological abnormalities associated with H. pylori were found to show changes in the species-specific and quantitative composition of the colonic microbiocenosis, which were symptomatic and revealed by bacteriological studies in 47.5% of cases and severe in 32.5%. When antihelicobacter therapy is planned, a through treatment of all family members and, if possible, pets should be made. Colonic microbiocenosis should be monitored while treating Helicobacter infection.

Endoscopic and clinical findings in first-degree relative of duodenal ulcer patients and control subjects.

The first-degree relatives of duodenal ulcer patients and of control probands were evaluated clinically and by gastroduodenal endoscopy for prevalence of duodenal ulcer. The control probands were randomly selected from a control population. 199 relatives of 51 duodenal ulcer probands were interviewed, and 154 of these were endoscoped. 154 control relatives who had been endoscoped were matched with the DU relatives according to sex and age. Endoscopic evidence of present or past duodenal or pyloric ulcer was present in 20 (13.0%) of the DU relatives and in only 6 (3.9%) of the control relatives (p less than 0.01). The frequency of macroscopic duodenitis and gastric erosions was also significantly higher (p less than 0.05) in DU relatives than in controls. A history of epigastric pain was obtained in 54 (35.1%) of endoscoped DU relatives and in 24 (15.6%) of control relatives (p less than 0.01). This study has shown an increased prevalence of endoscopic evidence of duodenal ulcer in the first-degree relatives of duodenal ulcer patients. The finding that duodenitis is also more prevalent in DU relatives than in controls support the view that duodenitis is linked with duodenal ulcer.