Absence Of Celiac Disease Research Articles

Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease

BackgroundAs one of the most common intestinal inflammatory diseases, celiac disease (CD) is typically characterized by an autoimmune disorder resulting from ingesting gluten proteins. Although the incidence and prevalence of CD have increased over time, the diagnostic methods and treatment options are still limited. Therefore, it is urgent to investigate the potential biomarkers and targeted drugs for CD.MethodsGene expression data was downloaded from GEO datasets. Differential gene expression analysis was performed to identify the dysregulated immune-related genes. Multiple machine algorithms, including randomForest, SVM-RFE, and LASSO, were used to select the hub immune-related genes (HIGs). The immune-related genes score (IG score) and artificial neural network (ANN) were constructed based on HIGs. Potential drugs targeting HIGs were identified by using the Enrichr platform and molecular docking method.ResultsWe identified the dysregulated immune-related genes at a genome-wide level and demonstrated their roles in CD-related immune pathways. The hub genes (MR1, CCL25, and TNFSF13B) were further screened by integrating several machine algorithms. Meanwhile, the CD patients were divided into distinct subtypes with either high- or low-immunoactivity using single-sample gene set enrichment analysis (ssGSEA) and consensus clustering. By constructing IG score based on HIGs, we found that patients with high IG score were mainly attributed to high-immunoactivity subgroups, which suggested a strong link between HIGs and immunoactivity of CD patients. In addition, the novel constructed ANN model showed the sound diagnostic ability of HIGs. Mechanistically, we validated that the HIGs play pivotal roles in regulating CD's immune and inflammatory state. Through targeting the HIGs, we also found potential drugs for anti-CD treatment by using the Enrichr platform and molecular docking method.ConclusionsThis study unveils the HIGs and elucidates the networks regulated by these genes in the context of CD. It underscores the pivotal significance of HIGs in accurately predicting the presence or absence of CD in patients. Consequently, this research offers promising prospects for the development of diagnostic biomarkers and therapeutic targets for CD.

Нецелиакийная чувствительность к глютену – диагностическая проблема в педиатрии

The possibility of a causal relationship between gluten intake and the development of symptoms in the absence of celiac disease (CD) and wheat allergy (WA) has recently gained new scientific interest and includes a condition known as non-celiac gluten sensitivity (NCGS). To date, NCGS has been widely described in adults, whereas there is little information about this pathology in pediatric practice. This article presents a clinical case of NCGS in a 6-year-old girl who was admitted to the gastroenterology department of the Republican Specialized Scientific and Practical Medical Center of Pediatrics (Republic of Uzbekistan) with complaints of abdominal pain, bloating, weight loss, liquid stools, headaches, and fatigue. The complaints appeared 5 months before hospitalization. Antibodies to tissue transglutaminase IgA were within reference ranges, specific IgE antibodies to wheat and gluten were not elevated. A biopsy from the distal duodenum revealed Marsh-Oberhuber 1 lesions. The patient was switched to a gluten-free diet (GFD) with suspected NCGS. At week 4 of the diet, an improvement was noted, but abdominal bloating persisted. An intolerance to components such as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) was suspected. The use of the FODMAP diet significantly improved the condition. The reintroduction of gluten after 6 weeks resulted in a recurrence of symptoms, confirming the diagnosis of NCGS. Given that the number of gluten-related diseases is increasing, and not much is known about NCGS, we decided to present this case to raise awareness and questions regarding diagnosis, the need for specific monitoring, and treatment. Key words: FODMAP, gluten, children, non-celiac gluten sensitivity, celiac disease

Non-Celiac Gluten Sensitivity and Protective Role of Dietary Polyphenols.

Pathogenetically characterized by the absence of celiac disease and wheat allergy, non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the consumption of gluten-containing foods that relieved by a gluten-free diet. Since it is very difficult to maintain a complete gluten-free diet, there is a high interest in discovering alternative strategies aimed at reducing gluten concentration or mitigating its toxic effects. Plant-based dietary models are usually rich in bioactive compounds, such as polyphenols, recognized to prevent, delay, or even reverse chronic diseases, including intestinal disorders. However, research on the role of polyphenols in mitigating the toxicity of gluten-containing foods is currently limited. We address the metabolic fate of dietary polyphenols, both as free and bound macromolecule-linked forms, with particular reference to the gastrointestinal compartment, where the concentration of polyphenols can reach high levels. We analyze the potential targets of polyphenols including the gluten peptide bioavailability, the dysfunction of the intestinal epithelial barrier, intestinal immune response, oxidative stress and inflammation, and dysbiosis. Overall, this review provides an updated overview of the effects of polyphenols as possible dietary strategies to counteract the toxic effects of gluten, potentially resulting in the improved quality of life of patients with gluten-related disorders.

Dietary recommendations of the French Society for Rheumatology for patients with chronic inflammatory rheumatic diseases.

This article presents the 1st set of dietary recommendations of the French Society for Rheumatology for patients suffering from chronic inflammatory rheumatic diseases (IRD) made by a working group consisting of 12 rheumatology experts, 3 physician nutrition specialists, 1 internal medicine specialist, 1 registered dietician and 3 representatives from patient associations. This group relied on a systematic literature review and on expert opinions, while taking into consideration not only the joint effects of diet in IRD but also the extra-articular ones. Eight general principles and nine recommendations were established. The general principles emphasize that nutritional advice is not a substitute for pharmacological treatment of IRD and that it is an integral part of the patients' overall care, which could help the patient actively participate in their care. The recommendations propose supporting weight loss in subjects who are overweight or obese, a Mediterranean-type diet and supplementation in polyunsaturated fatty acids, mainly omega-3. Conversely, gluten-free diets (in the absence of celiac disease), vegetarian/vegan diets, fasting and elimination of dairy products should not be proposed. Supplementation with vitamins or trace elements is not indicated for controlling chronic IRD activity, while the use of probiotics or spices is not recommended given the limited or disparate data.

Non-Celiac Gluten Sensitivity: An Update.

Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by the absence of celiac disease and wheat allergy in patients that trigger reproducible symptomatic responses to gluten-containing foods consumption. Due to the lack of sensitive and reproducible biomarkers for NCGS diagnosis, placebo-controlled gluten challenges must be carried out for its diagnosis. The gluten challenges can be either double- or single-blind, for research or clinical practice purposes, respectively. For improving our understanding about the magnitude and relevance of NCGS in different populations, epidemiological studies based on self-report have been carried out. However, the gluten challenge-based prevalence of NCGS remains to be estimated. Since NCGS was recently recognized as a clinical entity, more studies are needed to delve into NCGS pathogenesis, for instance, the molecular interactions between the suspected cereal grain components that trigger NCGS, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and amylase and trypsin inhibitors, and the immune system remains to be elucidated. Although still under debate, NCGS patients can be susceptible to only one or more than one of the NCGS triggers. The treatment of NCGS involves the dietary restriction of the suspected triggers of the disease, but there is controversial data about the effectiveness of different dietary interventions such as the gluten-free diet and low-FODMAP diet. Certainly, our understanding of NCGS is improving quickly due to the constant availability of new scientific information on this topic. Thus, the aim of the present narrative review is to present an up-to-date overview on NCGS from epidemiology to current therapy.

Long-term Intake of Gluten and Cognitive Function Among US Women

Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease. To examine whether gluten intake is associated with cognitive function in women without celiac disease. This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021. Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment. Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance. The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: -0.02; 95% CI, -0.07 to 0.03; P for trend = .22; learning and working memory: 0.02; 95% CI, -0.03 to 0.07; P for trend = .30; global cognition: -0.002; 95% CI, -0.05 to 0.05; P for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments. In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.

Neurological manifestation of coeliac disease with particular emphasis on gluten ataxia and immunological injury: a review article.

Coeliac disease (CD) is a gluten-induced enteropathy affecting 1% of the population and has extra intestinal manifestations. One such expression involves nervous system, and CD may present as gluten ataxia (GA), peripheral neuropathy and epileptiform disorder among others. Considerable controversy exists on the exact pathophysiological mechanism of gluten leading to ataxia. It is, however, clear that in intestinal axis tissue transglutaminase 2 (tTG2) is the primary target but in the nervous system, tTG6 may be the causative antigen although its exact role is not clear. Furthermore, it has also been postulated that anti-gangliodise antibodies may play a role in the emergence of central pathology if not the key contender. Moreover, the association of neurological injury with non-coeliac gluten sensitivity (NCGS), a related but pathologically different condition implies an independent mechanism of neuronal injury by gluten in the absence of CD. This review will touch on the salient features of CD and the nervous system and will highlight current controversies in relation to gluten and GA.

Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity?

The gluten-free diet (GFD) has gained increasing popularity in recent years, supported by marketing campaigns, media messages and social networks. Nevertheless, real knowledge of gluten and GF-related implications for health is still poor among the general population. The GFD has also been suggested for non-celiac gluten/wheat sensitivity (NCG/WS), a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of celiac disease (CD) or wheat allergy (WA). NCG/WS should be regarded as an “umbrella term” including a variety of different conditions where gluten is likely not the only factor responsible for triggering symptoms. Other compounds aside from gluten may be involved in the pathogenesis of NCG/WS. These include fructans, which are part of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA) and glyphosate. The GFD might be an appropriate dietary approach for patients with self-reported gluten/wheat-dependent symptoms. A low-FODMAP diet (LFD) should be the first dietary option for patients referring symptoms more related to FODMAPs than gluten/wheat and the second-line treatment for those with self-reported gluten/wheat-related symptoms not responding to the GFD. A personalized approach, regular follow-up and the help of a skilled dietician are mandatory.

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.

Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity

ObjectiveNon-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers...

22. Correlation between endoscopic and microscopic appearance in lymphocytic gastritis

Background: Lymphocytic gastritis (LG) is an inflammatory condition of the stomach characterised by an intraepithelial lymphocytosis of greater than 20 T lymphocytes per 100 surface epithelial cells. It has known associations with coeliac disease, H. pylori infection, viral infection, Crohn’s disease and gastric lymphoma. In many cases no cause is identified. The classic endoscopic description of lymphocytic gastritis is that of a varioloform gastritis seen at endoscopy, however the proportion of cases showing this feature is not known. Aims: To determine whether the various causes of lymphocytic gastritis show distinctive endoscopic changes that could be helpful in determining the cause of the intraepithelial lymphocytosis. Methods: Retrospective analysis of all cases of lymphocytic gastritis diagnosed at Envoi Specialist Pathologists from 2008–2018 where a description of the endoscopic appearance of the gastric mucosa was documented. Patient age and gender was collected. The endoscopic description was recorded as normal, mild non-specific gastritis, or erosive gastritis. This was then correlated with the presumptive cause for the LG. Results and conclusions: 311 cases of LG with endoscopic description of the gastric mucosa were identified. Erosive gastritis was seen in 124 of these cases. Erosive gastritis corelated with male sex (60 vs 44.4%, p=0.0107), older age (56.1 vs 51.8 years, p=0.017) and absence of coeliac disease on duodenal biopsy (85% vs 66%, p=0.0002). The endoscopic appearance did not correlate with resolution of lymphocytosis in 74 cases with follow-up biopsy (6 vs 17%, p=0.15). These findings show that coeliac disease is associated with minimal gastric changes in cases with concomitant LG and this could be used to suggest the diagnosis where no duodenal biopsy is supplied.

P705 Dietary practices and beliefs of patients with older-onset inflammatory bowel disease: A prospective UK study

Abstract Background In an aging population, 25–35% of those with inflammatory bowel disease (IBD) are over 60 years old. A third of these are diagnosed at or over the age of 60 (older-onset IBD). Virtually no studies exist exploring the dietary practices and beliefs of patients with older-onset IBD. Elderly patients with IBD are at increased risk of nutritional deficiency and associated complications making it all the more important to understand the dietary habits and self-imposed restrictions of this group. Methods A prospective, cross-sectional, questionnaire-based study is being conducted across NHS Trusts within the UK. Two-hundred patients with older-onset IBD will be recruited to complete a questionnaire regarding demographics and dietary practices. Here we provide an interim analysis of the data collected from the first 75 patients. Results Mean patient age is 73 years, 51% are male and 95% Caucasian. 68% have ulcerative colitis. Mean disease duration is 6 years. Thirty-six per cent of patients believe diet was an initiating factor in their IBD and this is based on their own experience (78%) or advice from a gastroenterologist (33%), dietitian (22%) or GP (22%). Fifty-six per cent of patients report a disease relapse in the last year and just under a third believe that diet could trigger a relapse. The most commonly identified triggers are spicy foods (61%), raw fruit and vegetables (57%), fatty foods (39%) and milk products (30%). Sixty-three per cent of patients avoid certain foods to prevent a relapse of IBD. The most commonly avoided foods are spicy (81%) and fatty foods (66%), carbonated drinks (60%), red meat (53%), raw fruit and vegetables (49%) and alcohol (49%). Half of patients report being able to find specific advice regarding dietary recommendations in IBD and 72% of these obtain this information from the internet. A quarter of patients avoid eating the same menu as their family at least some of the time to prevent relapse of their IBD and 36% of patients avoid eating out. One in five patients has tried a specific exclusionary diet to help manage their symptoms, most commonly a gluten free diet, in the absence of coeliac disease, in 12% of patients. Conclusion Despite a relatively low proportion of older-onset IBD patients believing diet is implicated in the initiation of their disease or its relapse, a significant number continue to restrict their diet. This, along with co-existing frailty, comorbidities and polypharmacy, may put this group of patients at increased risk of nutritional deficiency and its associated complications as well as impacting upon quality of life. Improved knowledge of the dietary habits of those with ‘older-onset’ IBD will allow healthcare professionals to identify those at risk and offer appropriate dietary interventions.

P612 Dietary practices and beliefs of British South Asians with inflammatory bowel disease: A prospective UK study

Abstract Background The increasing incidence of inflammatory bowel disease (IBD) in newly industrialised countries and immigrant populations appears to outpace that which genetic influences alone could instigate. Environmental factors, in particular, the western diet, are therefore implicated in its aetiopathogenesis. Limited data exist on the dietary practices of the migrant South Asian population with IBD. We aim to describe the dietary practices of British South Asian IBD patients and information resources utilised to guide these beliefs. Methods A prospective, cross-sectional, questionnaire-based study is being conducted across hospitals in the UK. Two-hundred South Asian patients with IBD are being recruited to complete a questionnaire regarding demographics and dietary practices. Results Data from 118 patients are available to date. Mean patient age is 43 years (51% female). Sixty-five per cent have ulcerative colitis (UC) and 33% Crohn’s disease (CD). Fifty-one per cent are of Indian ethnicity, 37% Pakistani and 10% Bangladeshi. Forty-nine per cent of patients were born in the UK to parents who were born outside of the UK and 51% of patients were born outside the UK. Mean disease duration is 10.5 years. Forty-six per cent considered diet to be an initiating factor in their IBD, based on their own experience (85%) as well as information from internet resources (31%) and other patients with IBD (19%). Fifty-nine per cent of patients felt that diet had triggered a relapse of their disease. Most commonly reported foods were spicy (69%) and fatty foods (47%), milk products (44%) and red meat (37%). Eighty-six per cent of patients avoided certain foods in an attempt to prevent an IBD ‘flare’. Most frequently avoided foods were spicy foods (76%), fatty foods (69%), red meat (60%), coffee (55%), carbonated drinks (54%) and milk products (53%). One in four patients had tried a specific exclusionary diet, with 13% having tried a gluten-free diet in the absence of coeliac disease, to manage their symptoms. Just over a half of patients reported being able to find specific dietary advice for IBD, most commonly via the internet. Over half of patients avoided eating the same meal as their family or eating out to prevent relapse of their IBD. 1 in 3 consumed certain foodstuffs or nutritional supplements to prevent a relapse of IBD, most commonly turmeric in 25% of these patients. Conclusion Dietary restriction may be highly prevalent amongst the British South Asian IBD community with a high proportion reporting diet as an initiating factor and trigger for disease flares. Studies on immigrant populations may hold valuable clues regarding the influence of migration, environmental influences and drift from traditional cultural practices on IBD aetiopathogenesis and related symptoms. A larger dataset will be presented at conference proceedings.

3227 Can a Gluten-Free Diet Be an Option in Treating Collagenous Colitis in the Absence of Celiac Disease?

INTRODUCTION: Collagenous colitis (CC), a subtype of Microscopic Colitis, is known to cause chronic diarrhea in the elderly. Steroid medication, particularly budesonide, has been rigorously studied and shown to be effective, leading to remission. Few studies have revealed the role diet has on decreasing these symptoms. CASE DESCRIPTION/METHODS: 69 y/o male with past medical history of chronic intermittent diarrhea for the past thirteen years. He initially presented with recurrence of non-bloody watery diarrhea, alternating with constipation and fecal incontinence for 2 weeks. Previous colonoscopy performed thirteen years ago revealed normal mucosa with diverticulosis. Further workup revealed a negative tTG- IgA, polypharmacy, or an infectious etiology. Labs were unremarkable. He underwent repeat colonoscopy, which demonstrated a fractured and nodular appearance of the cecum and ascending colon with small tears. Biopsies showed a focal increase in intraepithelial lymphocytes with a positive trichrome stain consistent with the diagnosis of CC. He was started on a GFD trial and had complete remission of his symptoms for three years. DISCUSSION: Chronic diarrhea affects approximately 5% of the population and at times can be challenging for gastroenterologists. When working up chronic diarrhea, microscopic colitis and celiac disease often play a large role. In this case, the patient was diagnosed with CC, however symptoms resolved on a GFD alone despite having multiple negative TTG levels. We believe that the multiple negative TTG levels were indicative of negative celiac disease. However, there is evidence showing that gluten can induce microscopic colitis. However, in women dietary gluten intake may not be a risk factor for the development of microscopic colitis in the absence of celiac disease. Nevertheless, the effects of gluten may be different in male veterans. CC is usually treated with a steroid based regimen, budesonide, to obtain remission. There are limited studies that have evaluated the impact that a GFD has upon the symptoms and histological findings in CC. Use of these medications can be associated with hyperglycemia, hypertension and metabolic bone disease which may be detrimental to the patient's health and prognosis. In conclusion, in patients diagnosed with CC consider starting a trial of GFD. Further studies are needed to evaluate the response of how a GFD affects the spectrum of severity in symptoms and histologic findings in patients diagnosed with CC, specifically in male veterans.

2954 Acute Pancreatitis Outcomes May Not Be Worse in Subjects Post-Liver Transplant

INTRODUCTION: The association of Acute Pancreatitis and Celiac Disease (CD) has been sparingly reported in the literature. CD is known to affect approximately 1% of the western population. A Swedish national database study reported a 3-fold increased risk of developing pancreatitis in patients with CD. The exact mechanism of this is unknown, but it could be related to an untreated celiac disease affecting the major papilla causing stenosis or exocrine pancreatic insufficiency that has been reported previously. This study aimed to look at the association between acute pancreatitis and celiac disease. We also looked at whether there was any association between chronic pancreatitis and celiac disease. METHODS: We performed a retrospective cross-sectional cohort study using the 2013 National Inpatient Sample (NIS) database. We included all patients who were hospitalized with either acute pancreatitis (ICD Code 577.0) or Chronic Pancreatitis (577.1). Patients who had diagnoses of both acute and chronic pancreatitis were considered to have acute on chronic pancreatitis and combined with the chronic pancreatitis group. We then analyzed both groups for the presence or absence of celiac disease. Continuous variables were compared using t-tests, and categorical variables were compared using Rao-Scott chi-square tests. All analyses were performed using SAS Survey Procedures (version 9.4, The SAS Institute, Cary, NC). RESULTS: We analyzed more than 35 million hospitalizations in 2013 out of which 378,715 had a primary discharge diagnosis of acute pancreatitis and 155,130 had a primary discharge diagnosis of chronic pancreatitis. The mean age in the acute pancreatitis group was 53.3 yrs and in chronic pancreatitis group was 51.7 yrs. There were more males in chronic pancreatitis group (55.1%) than females (44.9%). There was significantly higher prevalence of acute pancreatitis in CD (2.3%) than non-CD patients (1.2%) (Figure 1, P = 0.001). Similarly, there was higher prevalence of chronic pancreatitis (1.2%) than the control group (0.43%) (Figure 1, P < 0.001). CONCLUSION: There is a higher prevalence of acute pancreatitis in patients with CD. Patients were also found to have much higher prevalence of chronic pancreatitis in CD. This could be related to recurrent acute pancreatitis episodes in CD patients. Further studies are needed to validate these findings.

2915 Acute Pancreatitis and Celiac Disease—Is There an Association?

INTRODUCTION: The association of Acute Pancreatitis and Celiac Disease (CD) has been sparingly reported in the literature. CD is known to affect approximately 1% of the western population. A Swedish national database study reported a 3-fold increased risk of developing pancreatitis in patients with CD. The exact mechanism of this is unknown but it could be related to untreated celiac disease affecting the major papilla causing stenosis or exocrine pancreatic insufficiency that has been reported previously. The aim of this study was to look at the association between acute pancreatitis and celiac disease. We also looked whether there was any association between chronic pancreatitis and celiac disease. METHODS: We performed a retrospective cross-sectional cohort study using the 2013 National Inpatient Sample (NIS) database. We included all patients who were hospitalized with either acute pancreatitis (ICD Code 577.0) or Chronic Pancreatitis (577.1). Patients who had diagnoses of both acute and chronic pancreatitis were considered to have acute on chronic pancreatitis and combined with the chronic pancreatitis group. We then analyzed both groups for presence or absence of celiac disease. Continuous variables were compared using t-tests and categorical variables were compared using Rao-Scott chi-square tests. All analyses were performed using SAS Survey Procedures (version 9.4, The SAS Institute, Cary, NC). RESULTS: We analyzed more than 35 million hospitalizations in 2013 out of which 378,715 had a primary discharge diagnosis of acute pancreatitis and 155,130 had a primary discharge diagnosis of chronic pancreatitis. The mean age in the acute pancreatitis group was 53.3 yrs and in chronic pancreatitis group was 51.7 yrs. There were more males in chronic pancreatitis group (55.1%) than females (44.9%). There was significantly higher prevalence of acute pancreatitis in CD (2.3%) than non-CD patients (1.2%) (Figure 1, P = 0.001). Similarly, there was higher prevalence of chronic pancreatitis (1.2%) than the control group (0.43%) (Figure 1, P < 0.001). CONCLUSION: There is a higher prevalence of acute pancreatitis in patients with CD. Patients were also found to have much higher prevalence of chronic pancreatitis in CD. This could be related to recurrent acute pancreatitis episodes in CD patients. Further studies are needed to validate these findings.

Adverse Reactions to Wheat or Wheat Components.

Wheat is an important staple food globally, providing a significant contribution to daily energy, fiber, and micronutrient intake. Observational evidence for health impacts of consuming more whole grains, among which wheat is a major contributor, points to significant risk reduction for diabetes, cardiovascular disease, and colon cancer. However, specific wheat components may also elicit adverse physical reactions in susceptible individuals such as celiac disease (CD) and wheat allergy (WA). Recently, broad coverage in the popular and social media has suggested that wheat consumption leads to a wide range of adverse health effects. This has motivated many consumers to avoid or reduce their consumption of foods that contain wheat/gluten, despite the absence of diagnosed CD or WA, raising questions about underlying mechanisms and possible nocebo effects. However, recent studies did show that some individuals may suffer from adverse reactions in absence of CD and WA. This condition is called non-celiac gluten sensitivity (NCGS) or non-celiac wheat sensitivity (NCWS). In addition to gluten, wheat and derived products contain many other components which may trigger symptoms, including inhibitors of α-amylase and trypsin (ATIs), lectins, and rapidly fermentable carbohydrates (FODMAPs). Furthermore, the way in which foods are being processed, such as the use of yeast or sourdough fermentation, fermentation time and baking conditions, may also affect the presence and bioactivity of these components. The present review systematically describes the characteristics of wheat-related intolerances, including their etiology, prevalence, the components responsible, diagnosis, and strategies to reduce adverse reactions.

A Gluten-Free Diet, Not an Appropriate Choice without a Medical Diagnosis.

In the past, only people diagnosed with celiac disease, approximately 1% of the population, avoided gluten consumption through all their meals. However, popular media often now mistakenly present gluten-free foods as being a healthier choice, and more people have now concluded that gluten is a harmful part of the diet. A review of literature on gluten-free diets, gluten sensitivity, celiac disease, and attitudes toward gluten consumption was undertaken to examine the prevalence and consequences of adopting a gluten-free diet and to provide guidance to healthcare practitioners whose patients are now often adopting this diet without medical input. Aside from celiac disease, nonceliac gluten sensitivity (NCGS) occurs in those persons in which gluten ingestion leads to symptomatic manifestations in the absence of celiac disease or wheat allergy but who report a remission of certain symptoms after removing gluten from their diet. However, it was been shown that a large percentage of people who claim NCGS do not feel those manifestations under a double-blind challenge to gluten. Moreover, some parents, believing that ingesting gluten is detrimental for their health, adopt gluten-free diets for their children. A review of existing data shows that there are detrimental effects to going gluten free, including loss of the dietary fiber, deficiencies in dietary minerals and vitamins, and potential heavy metal exposure. Healthcare practitioners should query patients about their dietary choices, and in cases of questionable adoption of gluten-free diet, patients and parents are educated about the detriments of a gluten-free diet, and in cases where patients continue to insist on gluten-free foods, referrals to nutritional counseling are warranted in order to minimize potential harm.

Gluten Vehicle and Placebo for Non-Celiac Gluten Sensitivity Assessment.

Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extraintestinal manifestations triggered after gluten ingestion in the absence of celiac disease and wheat allergy. Because of the lack of biomarkers for NCGS diagnosis, the cornerstone for its assessment is a single- or double-blind placebo-controlled (DBPC) gluten challenge. However, there are some non-standardized points in the diagnostic approach proposed by the experts. This complicate comparisons among the results published by different research groups. The gluten vehicle and placebo must be indistinguishable from each other, which entails sensory and technological evaluations of the designed gluten vehicle and placebo products. At the moment, there is no standardized method for the preparation of the gluten vehicle and placebo for carrying out DBPC gluten challenges for NCGS assessment. This review focuses on the challenges that researchers have to face, either for the development of an accepted gluten vehicle and placebo or for identifying NCGS cases on the basis of DBPC gluten challenges.

IRRITABLE BOWEL SYNDROME, FOOD INTOLERANCE AND NON- CELIAC GLUTEN SENSITIVITY. A NEW CLINICAL CHALLENGE.

Approximately 80% of irritable bowel syndrome (IBS) patients report that their symptoms are triggered after ingesting one or specific food groups. Gluten, wheat and related proteins (e.g., amylase-trypsin inhibitors, and fermentable oligo-di-mono-saccharides and polyols (FODMAPs) are the most relevant IBS symptom triggers, although the true 'culprit(s)' is/are still not well established. The concept of causal relationship between gluten intake and the occurrence of symptoms in the absence of celiac disease and wheat allergy was termed non-celiac gluten sensitivity (NCGS). The borderline between celiac disease, wheat allergy, IBS and NCGS is not always clearly distinguishable, and the frequency and clinical identity of NGCS are still unclear. An overlap between IBS and NCGS has been detected. The incomplete knowledge of the etiopathogenesis of these clinical conditions, lack of data on their real epidemiology, as well as the absence of a gold standard for their diagnosis, make the overall picture difficult to understand "It is crucial to well define the interaction between IBS, food intolerance and NGCS, since the role of diet in IBS and its dietary management is an essential tool in the treatment of a large number of these patients". The objective of the present review is to provide an overview highlighting the interaction between IBS, food intolerance and NCGS in order to unravel whether gluten/wheat/FODMAP sensitivity represents 'facts' and not 'fiction' in IBS symptoms.