Efficacy of 1 L polyethylene glycol plus ascorbate versus 4 L polyethylene glycol in split-dose for colonoscopy cleansing in out and inpatient: A multicentre, randomized trial (OVER 2019).

BACKGROUND AND AIMS: Adequate bowel cleansing is essential for colonoscopy quality. A novel 1 L polyethylene glycol plus ascorbate (1 L PEG+ASC) solution has been recently introduced. Nevertheless, the efficacy of 1 L PEG+ASC as compared to that of high-volume bowel preparation in both inpatients and outpatients is still unclear. PATIENTS AND METHODS: This single-blinded, non-inferiority study randomized patients undergoing colonoscopy to receive split-dose 1 L PEG+ASC or 4 L PEG. The primary endpoint was the overall cleansing success. Secondary endpoints were excellent cleansing and high-quality cleansing of the right colon, as well as lesions detection rate, patient compliance, tolerability and safety. RESULTS: Overall, 478 patients were randomized to 1 L PEG+ASC (N = 236) or 4 L PEG (N = 242). The 1 L PEG+ASC showed higher cleansing success rate (91.8% vs 83.6%; P=0.01) and a high-quality cleansing of the right colon (52.3% and 38.5%; P=0.004) compared to 4 L PEG. Moreover, 1 L PEG+ASC achieved a higher cleansing success in out-patients (96.3%% vs 88.6%; P=0.018), and a similar success rate in the in-patients (84.7% vs 76.7%; P=0.18). Adenoma detection rate, tolerability and incidence of adverse events were comparable between preparations. CONCLUSIONS: The 1 L PEG+ASC showed higher efficacy in achieving adequate colon cleansing compared with 4 L PEG, particularly in the right colon. No differences in the tolerability and safety were detected.

Association between neuropeptides and mucins in Crohn's disease mucous cells.

Crohn's disease (CD) and ulcerative colitis (UC) are both inflammatory bowel diseases (IBD). Unlike UC, which is limited to the mucosa of the colon, CD inflammation is characterized by chronic mucosal ulcerations affecting the entire gastrointestinal tract. Goblet cells (GCs) can be found in some lining epithelia, particularly in the respiratory and digestive tracts. GCs represent the main source of mucin that are the significant components of the mucus layer; hypertrophy of GCs and an increase in mucin production are observed in many enteric infections. The cytoplasm of goblet cells may also contain neuropeptides, such as serotonin, that can be altered in inflammatory bowel disease (IBD). The defense system of the gut is represented by the intestinal mucosal barrier, its protective function is strictly connected to the regulation of the mucus layer and the coordination of the neuro-immune response. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease, were analyzed by immunostaining for MUC2, MUC4, 5-HT, and VAChT. This study aims to define the link between neuropeptides and mucins in mucous cells and their involvement in the inflammation process. Our results showed in mucous cells of Crohn's disease (CD) patients a high expression of MUC4 and a decrease in the expression of vesicular acetylcholine transporter (VAChT) demonstrating the presence of an inflammatory state.

Effectiveness and application of artificial intelligence for endoscopic screening of colorectal cancer: the future is now.

INTRODUCTION: Artificial intelligence (AI) in gastrointestinal endoscopy includes systems designed to interpret medical images and increase sensitivity during examination. This may be a promising solution to human biases and may provide support during diagnostic endoscopy. AREAS COVERED: This review aims to summarize and evaluate data supporting AI technologies in lower endoscopy, addressing their effectiveness, limitations, and future perspectives. EXPERT OPINION: Computer-aided detection (CADe) systems have been studied with promising results, allowing for an increase in adenoma detection rate (ADR), adenoma per colonoscopy (APC), and a reduction in adenoma miss rate (AMR). This may lead to an increase in the sensitivity of endoscopic examinations and a reduction in the risk of interval-colorectal cancer. In addition, computer-aided characterization (CADx) has also been implemented, aiming to distinguish adenomatous and non-adenomatous lesions through real-time assessment using advanced endoscopic imaging techniques. Moreover, computer-aided quality (CADq) systems have been developed with the aim of standardizing quality measures in colonoscopy (e.g. withdrawal time and adequacy of bowel cleansing) both to improve the quality of examinations and set a reference standard for randomized controlled trials.

Over-the-scope Technique for Partially Covered Self-expandable Metal Stent Placement to Treat Duodenal Perforation during EUS.

BACKGROUND AND AIMS: Although endoscopic ultrasound (EUS) is generally safe, duodenal perforation may occur during the procedure. When the iatrogenic break is wide, endoscopic positioning of a covered self- expandable metal stent is indicated to avoid a more invasive surgical approach. We evaluated the efficacy of the 'over-the-scope stenting' (OTSS) technique to treat iatrogenic duodenal perforations occurred during EUS. METHODS: Data of patients with large iatrogenic duodenal perforations treated with OTSS procedure were collected in 5 centers. Technical success was defined as a correct stent placement on the perforation site, and clinical success as complete healing of the duodenal leak at stent removal 3 weeks later. RESULTS: A total of 15 (7 males; median age: 78 years, range 47-91) patients were included in this series. A correct stent positioning was achieved in all cases (technical success: 100%), and the perforation was healed in all, apart from one patient at stent removal (clinical success: 93%). This patient was successfully treated with a novel stent placement. No immediate post-procedural adverse events occurred, and no need for emergency surgery was recorded. In one (6.7%) patient, stent migration occurred 10 days after positioning, and it was spontaneously expulsed with stool movement without complications two days later. CONCLUSIONS: Our data showed that the OTTS technique for partially covered self-expandable metal stent placement is feasible, safe and effective to tread large iatrogenic duodenal perforation occuring during EUS.

Diagnosis and Management of Esophagogastric Varices.

Acute variceal bleeding (AVB) is a potentially fatal complication of clinically significant portal hypertension and is one of the most common causes of acute upper gastrointestinal bleeding. Thus, esophagogastric varices represent a major economic and population health issue. Patients with advanced chronic liver disease typically undergo an upper endoscopy to screen for esophagogastric varices. However, upper endoscopy is not recommended for patients with liver stiffness < 20 KPa and platelet count > 150 × 109/L as there is a low probability of high-risk varices. Patients with high-risk varices should receive primary prophylaxis with either nonselective beta-blockers or endoscopic band ligation. In cases of AVB, patients should receive upper endoscopy within 12 h after resuscitation and hemodynamic stability, whereas endoscopy should be performed as soon as possible if patients are unstable. In cases of suspected variceal bleeding, starting vasoactive therapy as soon as possible in combination with endoscopic treatment is recommended. On the other hand, in cases of uncontrolled bleeding, balloon tamponade or self-expandable metal stents can be used as a bridge to more definitive therapy such as transjugular intrahepatic portosystemic shunt. This article aims to offer a comprehensive review of recommendations from international guidelines as well as recent updates on the management of esophagogastric varices.

Endoscopic Ultrasound Advanced Techniques for Diagnosis of Gastrointestinal Stromal Tumours.

Gastrointestinal Stromal Tumors (GISTs) are subepithelial lesions (SELs) that commonly develop in the gastrointestinal tract. GISTs, unlike other SELs, can exhibit malignant behavior, so differential diagnosis is critical to the decision-making process. Endoscopic ultrasound (EUS) is considered the most accurate imaging method for diagnosing and differentiating SELs in the gastrointestinal tract by assessing the lesions precisely and evaluating their malignant risk. Due to their overlapping imaging characteristics, endosonographers may have difficulty distinguishing GISTs from other SELs using conventional EUS alone, and the collection of tissue samples from these lesions may be technically challenging. Even though it appears to be less effective in the case of smaller lesions, histology is now the gold standard for achieving a final diagnosis and avoiding unnecessary and invasive treatment for benign SELs. The use of enhanced EUS modalities and elastography has improved the diagnostic ability of EUS. Furthermore, recent advancements in artificial intelligence systems that use EUS images have allowed them to distinguish GISTs from other SELs, thereby improving their diagnostic accuracy.

Digital single-operator cholangioscopy in treating difficult biliary stones: results from a multicenter experience.

BACKGROUND: In clinical practice, standard endoscopic treatment of biliary stones fails in up to 10% of patients, and more invasive procedures such as percutaneous trans-hepatic interventions or surgery might become necessary. The aim of this multicenter retrospective study, based on prospectively-collected data, was to evaluate both the efficacy and the safety of digital-single operator cholangioscopy (D-SOC) to treat difficult biliary stones in cases with a previous failure of conventional endoscopic methods. METHODS: Only patients with a previous failure of endoscopic standard treatment and a D-SOC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone clearance rate per procedure and per patient. RESULTS: Out of 1258 ERCP performed at our centers, 31 cholangioscopes in 21 patients were solely performed for the treatment of difficult biliary stones using EHL or LL. A complete biliary stone removal was achieved in 67.7% (21/31) of all procedures including initial and repeated examinations, while in 35.4% (11/31) of all procedures an incomplete removal was accomplished of which 36.3% had a partial stone removal. In 22 procedures EHL was adopted as techniques to fragment and remove biliary stones, while in 9 procedures LL was used. In both the techniques, the complete stone removal rate and the incomplete stone removal rate were similar (75% vs. 77.7%, P>0.05). Furthermore, the success rate of digital D-SOC to treat difficult biliary stones was assessed per patient: overall, 100% of patients with difficult biliary stones were successfully treated using D-SOC. Only one patient experienced mild cholangitis classified ad mild adverse event following ASGE (American Society of Gastrointestinal Endoscopy) lexicon. CONCLUSIONS: Our data indicate that digital D-SOC assisted biliary stone treatment is highly efficient for the treatment of difficult biliary stones even in such patients in whom previous conventional endoscopic methods to treat biliary stones have failed. Therefore, D-SOC might be considered the new standard of care for these patients, being both, effective and safe.

Predictive Factors of Adequate Bowel Cleansing for Colonoscopy in the Elderly: A Retrospective Analysis of a Prospective Cohort.

Factors affecting the quality of bowel preparation for colonoscopy in the elderly are not fully known, and current guidelines provide no specific recommendations. This study aimed to assess the difference in bowel cleansing in young and elderly patients and evaluate predictors of bowel cleansing in the elderly. We retrospectively reviewed a prospective cohort of 1289 patients performing colonoscopy after a 1-, 2-, or 4-L PEG-based preparation. All 1289 were included in the analysis. Overall, 44.6% of patients were aged ≥65 years. Cleansing success (CS) was achieved in 77.3% and 70.3% of patients aged <65 years and ≥65 years, respectively. At multivariable analysis, split regimen (OR = 2.43, 95% CI = 1.34−4.38; p = 0.003), adequate cleansing at previous colonoscopy (OR = 2.29, 95% CI = 1.14−4.73; p = 0.02), tolerability score (OR = 1.29, 95% CI = 1.16−1.44; p < 0.001), a low-fiber diet for at least 3 days (OR = 2.45, 95% CI = 1.42−4.24; p = 0.001), and colonoscopy within 5 h after the end of preparation (OR = 2.67, 95% CI = 1.28−5.56; p = 0.008) were independently associated with CS in the elderly. Combining a low-fiber diet for at least 3 days, split preparation, and colonoscopy within 5 h allowed a CS rate above 90% and should always be encouraged. A 1-L PEG-ASC preparation was also associated with greater high-quality cleansing of the right colon and may be preferred.

Corrigendum: Adenosine receptor stimulation by polydeoxyribonucleotide improves tissue repair and symptomology in experimental colitis.

[This corrects the article DOI: 10.3389/fphar.2016.00273.].

COVID-19 and the Pancreas: A Narrative Review.

The outbreak of COVID-19, initially developed in China in early December 2019, has rapidly spread to other countries and represents a public health emergency of international concern. COVID-19 has caused great concern about respiratory symptoms, but it is worth noting that it can also affect the gastrointestinal tract. However, the data on pancreatic involvement during SARS-CoV-2 infection are limited. The prevalence and severity of pancreatic damage and acute pancreatitis, as well as its pathophysiology, are still under debate. Moreover, the possible implication of pancreatic damage as an apparent adverse effect of COVID-19 therapies or vaccines are issues that need to be addressed. Finally, the COVID-19 pandemic has generated delays and organizational consequences for pancreatic surgery, an element that represent indirect damage from COVID-19. This narrative review aims to summarize and analyze all the aspects of pancreatic involvement in COVID-19 patients, trying to establish the possible underlying mechanisms and scientific evidence supporting the association between COVID-19 and pancreatic disease.

Recognizing the Emergent and Submerged Iceberg of the Celiac Disease: ITAMA Project-Global Strategy Protocol.

Coeliac disease (CD) is frequently underdiagnosed with a consequent heavy burden in terms of morbidity and health care costs. Diagnosis of CD is based on the evaluation of symptoms and anti-transglutaminase antibodies IgA (TGA-IgA) levels, with values above a tenfold increase being the basis of the biopsy-free diagnostic approach suggested by present guidelines. This study showcased the largest screening project for CD carried out to date in school children (n=20,000) aimed at assessing the diagnostic accuracy of minimally invasive finger prick point-of-care tests (POCT) which, combined with conventional celiac serology and the aid of an artificial intelligence-based system, may eliminate the need for intestinal biopsy. Moreover, this study delves deeper into the "coeliac iceberg" in an attempt to identify people with disorders who may benefit from a gluten-free diet, even in the absence of gastrointestinal symptoms, abnormal serology and histology. This was achieved by looking for TGA-IgA mucosal deposits in duodenal biopsy. This large European multidisciplinary health project paves the way to an improved quality of life for patients by reducing the costs for diagnosis due to delayed findings of CD and to offer business opportunities in terms of diagnostic tools and support.

Role of Serotonin in the Maintenance of Inflammatory State in Crohn's Disease.

Crohn's disease (CD) is a chronic intestinal inflammation considered to be a major entity of inflammatory bowel diseases (IBDs), affecting different segments of the whole gastrointestinal tract. Peripheral serotonin (5-HT), a bioactive amine predominantly produced by gut enterochromaffin cells (ECs), is crucial in gastrointestinal functions, including motility, sensitivity, secretion, and the inflammatory response. These actions are mediated by a large family of serotonin receptors and specialized serotonin transporter (SERT) located on a variety of cell types in the gut. Several studies indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease were analyzed by immunostaining for serotonin, Langerin/CD207, and alpha-Smooth Muscle Actin (α-SMA). As controls, unaffected (normal) intestinal specimens of seven individuals were investigated. This study aimed to show the expression of serotonin in dendritic cells (DCs) and myofibroblast which have been characterized with Langerin/CD207 and α-SMA, respectively; furthermore, for the first time, we have found the presence of serotonin in goblet cells. Our results show the correlation between different types of intestinal cells in the maintenance of the inflammatory state in CD linked to the recall of myofibroblasts.

Use of catheter-based cholangioscopy in the diagnosis of indeterminate stenosis: a multi-centre experience.

BACKGROUND: Direct bile ducts visualization through cholangioscopy has gained popularity due to its better diagnostic accuracy than a standard ERCP in indeterminate biliary stricture. AIM: We aimed to review our catheter-based cholangioscopy interventions in patients with indeterminate biliary stenosis, using the SpyGlass Direct Visualization System (SDVS) and summarize our experience in terms of procedures and results. RESULTS: we collected 25 consecutive patients with indeterminate biliary stricture over 3 years. The overall procedural success in our cohort amounted to 96% (24/25). If we focus on the diagnostic procedures, the ability to merely visualize the region of interest/lesion and perform biopsy of the lesion was possible in 96 % (24/25) In our cohort localization in the common bile duct (P = 0.03; 95 % CI 0.27-0.96) was found as positive determining factor for diagnosis. Sensitivity, specificity and accuracy for visual diagnosis by SDVS in our cohort were 100, 83.3 and 96 %, respectively. The use of biopsy or obtaining a histological diagnosis to assist in identifying patients with malignant stenosis, to exclude malignancy and to correctly classify diagnosed patients resulted in a sensitivity of 100 %, a specificity of 73% % with an overall accuracy of 94.4 %. Only a mild adverse event (cholangitis, treated conservatively) occurred. CONCLUSIONS: Today, the SDVS should be considered essential in diagnosing indeterminate biliary strictures, since the procedure is associated with high procedural success in terms of diagnostic accuracy, alters clinical outcome in over 80 % of considered insolvable cases, with an acceptable safety profile.

Managing Pediatric Foreign Body Ingestions: A 10-Year Experience.

BACKGROUND: Foreign body (FB) ingestion is a common global issue in pediatrics. Most of the ingested FBs pass through the gastrointestinal tract, but up to 20% of cases require endoscopic removal. In this study, we retrospectively reviewed all pediatric cases of FB ingestion requiring endoscopic removal over a 10-year period in a tertiary hospital to compare the symptoms at presentation and outcomes with those reported in previous studies and to assess the association of the outcomes with patient and FB characteristics. METHODS: A retrospective chart review of children 16 years or younger who underwent upper endoscopy for FB ingestion from 2008 to 2018 in a tertiary hospital was included. Data on demographics, clinical presentation, characteristics of FBs, endoscopic findings, and outcomes were reviewed. The clinical data were further evaluated to determine the circumstances surrounding FB ingestion, FB management, and patient outcomes. Descriptive analysis of the data was performed using medians, frequencies, and percentage; χ2 or Fisher exact test was used to assess the dependence between categorical variables. RESULTS: Eighty-six patients (median age, 5.1 years; 67% males) underwent endoscopy for suspected FB ingestion, with a confirmation rate of 91%. Coins were the most commonly ingested FBs (n = 49, 57%). Most patients were symptomatic (84%); 97% of patients in whom the FB had an esophageal location and all patients in whom the FB was not detected by endoscopy were symptomatic (P = 0.007). The most frequent symptoms were drooling (70%) and unexplained crying (48%). Unexplained crying was more common in younger than in older patients (P < 0.001). The FB was more likely to be located in the esophagus in patients with drooling (P < 0.001) and dysphagia (P < 0.001). The distribution of FB location differed according to the FB type, with coins most frequently located in the esophagus and sharp and other FBs in the stomach (P = 0.023). Only 7 patients (8%) developed mild FB-related mucosal injury. No complications occurred during FB removal. All patients had an uneventful outcome. CONCLUSIONS: Foreign body ingestion is common among younger children, and the clinical presentation can be variable. The presence or absence of symptoms, as well as the type of symptom, could aid clinicians in implementing diagnosis and proper management approaches in patients who ingest FBs requiring endoscopy.

Performance of EUS-FNB in solid pancreatic masses: a lesson from 463 consecutive procedures and a practical nomogram.

The study's main goal was the diagnostic adequacy of pancreatic endoscopic ultrasonographic (EUS) fine-needle biopsy (FNB) and associated predictive factors. The secondary objective was to define the diagnostic accuracy of EUS-FNB in the diagnosis of pancreatic masses and pancreatic malignancies. None of the studies reported the diagnostic adequacy and accuracy of EUS. We retrospectively identified patients with solid pancreatic lesions that underwent EUS-FNB between 2013, and 2018. We calculated diagnostic adequacy and related factors. Using definitive histology on the surgically resected specimen as the gold standard, we calculated diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNB. We identified a total of 463 procedures. Diagnostic specimens were adequate in 436 procedures (94.1%), while 27 biopsies provided insufficient samples (5.9%). The multivariate analysis showed that lesion size and needle caliper were the only factors influencing diagnostic adequacy. The use of a biopsy needle (OR 0.69, 95% CI 0.30-0.1.63, P 0.400) did not improve sample adequacy. We calculated sensitivity (100%), specificity (93.2%), diagnostic accuracy (93.2%), positive predictive value (97.1%), and negative predictive value (100%) using resected specimen as the gold standard. We found no significant complications. EUS-FNB is a reliable technique for the histological characterization of solid pancreatic masses.

An Unusual Presentation of Crohn's Disease Diagnosed Following Accidental Ingestion of Fruit Pits: Report of Two Cases and Review of the Literature.

The clinical course of Crohn's disease (CD) is often complicated by intestinal strictures, which can be fibrotic, inflammatory, or mixed, therefore leading to stenosis and eventually symptomatic obstruction. We report two cases of subclinical CD diagnosed after fruit pit ingestion, causing bowel obstruction; additionally, we conducted a narrative review of the scientific literature on cases of intestinal obstruction secondary to impacted bezoars due to fruit pits. Symptoms of gastrointestinal bezoars in CD patients are not diagnostic; and the diagnosis should be based on a combined assessment of history, clinical presentation, imaging examination and endoscopy findings. This report corroborates the concept that CD patients are at a greater risk of bowel obstruction with bezoars generally and shows that accidental ingestion of fruit pits may lead to an unusual presentation of the disease. Therapeutic options in this group of patients differ from the usual approaches implemented in other patients with strictures secondary to CD.

Microbiota Gut-Brain Axis in Ischemic Stroke: A Narrative Review with a Focus about the Relationship with Inflammatory Bowel Disease.

The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer's disease, and Parkinson's disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidencesconcerningthe role of the gut-brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut-brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke.

Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms.

Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.

Lipomatosis of the ileocecal valve: A not to miss diagnosis when performing magnetic resonance enterography.

Lipomatosis of ileocecal valve is a rare condition that can be missed using the standard protocol of Magnetic Resonance Enterography. Additional T1-weighted scans without fat saturation can be helpful when adipose lesions of the bowel are suspected.

Expression of VAChT and 5-HT in Ulcerative colitis dendritic cells.

Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract that can affect people of worldwide. In contrast with Crohn's disease, that can relate the entire thickness of the bowel wall, the inflammation of ulcerative colitis is limited to the colonic mucosa. Immune cells including activated T cells, plasma cells, mast cells, macrophages, and dendritic cells (DCs) trigger the inflammation. Furthermore, dendritic cells are antigen presenting cells involved in maintaining intestinal immune homeostasis. It has been described an increment of number in DCs colonic mucosa of patients with ulcerative colitis. The immune cells such as antigen-presenting cells can act as autocrine or paracrine modulators. Recent studies showed that dendritic cells synthetized and released classical neurotransmitters as glutamate, dopamine, acetylcholine, and serotonin. Paraformaldehyde-fixed intestinal tissues, obtained from the stricture sites of ten patients with ulcerative colitis were analyzed by immunostaining for Langerin/CD207, serotonin and vesicular acetylcholine transporter. As controls, unaffected (normal) portions of five patients were also investigated. Aim of this study was to characterize for the first time the human gut dendritic cells of ulcerative colitis patients, with Langerin/CD207 that is a c-type lectin expressed by different types of DCs and to colocalize in the same cells the expression of serotonin and vesicular acetylcholine transporter, showing the link between dendritic cells, gut enterochromaffin cells or autonomic nerves in immune activation and generation of intestinal inflammation.