Gluten contamination, even within the frame of a strict GFD, cannot be entirely avoided: Plenty of products contain hidden gluten, such as sausages, soups, soy sauce and ice cream. But even in gluten-free-labeled products there are traces of gluten. This is mostly due to cross-contamination with gluten-containing products that are processed or stored in the same place [ 9 ]. The term “gluten-free” thus generally refers to an amount of gluten that is thought to be harmless and does not imply total absence of gluten. In fact, the amount of gluten deriving solely from cross-contamination in a supposedly GFD may range from 5 to 50 mg per day [ 10 , 11 ]. The level of gluten content in food products is expressed as parts per million (ppm, corresponding to mg/kg). Gibert et al., collected consumption data of gluten-free products by CD patients in order to estimate the average gluten exposure of celiac patients who follow a GFD. Taking into account different dietary habits in European countries (Norway, Germany, Italy, Spain) they concluded that a limit of 20 ppm for products naturally gluten-free and 100 ppm for products rendered gluten-free would be acceptable [ 12 ]. According to the current guidelines of the European Commission a commercially sold product may be called “gluten-free” if it contains less than 20 ppm gluten (20mg/kg) [ 13 ].
gastrointestinal tract which is affected, individuals with celiacdisease may experience symptoms such as cramping, abdominal pain, diarrhea and gas production. Also, celiacdisease can cause adverse effects to other parts of the body including bone or joint pain, numbness in the legs, ulcers in the mouth and itchiness and blisters on the skin known as dermatitis herpetiformis (12). While these are the common symptoms of celiacdisease, some people may not experience any of the classical symptoms, but instead present with problems such as iron deficiency anemia, infertility, osteoporosis, unexplained weight loss, and short stature (9, 12). These individuals are classified as having “silent” or “latent” celiacdisease and test positive for certain antibodies, but show no evidence of villous atrophy or other intestinal damage (12).
Therefore, we argue that having celiacdisease can be seen as a lack in resources as well, because of two reasons. First, the glutenfreediet can be difficult to follow and can be experienced as restrictive  . A dietary restriction such as a glutenfreediet can have a negative impact on the ability to dine out, eat at a friend’s place or travel  . The restrictions that a glutenfreediet imposes on eating outside of the home may impact someone’s opportunities to socialize, since social events often involve food. This could reduce the informal social capital of people who suffer from celiacdisease or NCGS. Second, celiacdisease is a chronic condition. Although complaints should be manageable by following a glutenfreediet, some people still experience health complaints [15,16] which can impose restrictions on people’s daily lives, including opportunities to gain and maintain informal social capital by participating in social events.
Our study also demonstrates differ- ences between children who more re- cently initiated a GFD compared with children who had been following a GFD for a longer period ( ⬎ 4 years). We used time on a GFD rather than age at CD diagnosis to categorize the popula- tion because for some children, the re- strictive diet and diagnosis did not oc- cur at the same time; however, a GFD does likely correspond closely to the length of time a child has had a diag- nosis of CD, so it can be used as a proxy for time of diagnosis. Our surveys dem- onstrated that camp had a positive ef- fect on all children in almost all quality-of-life categories. The effect was more prominent for children who more recently had started a GFD ( ⱕ 4 years). Children who had been on a GFD for a longer period had more over- all positive ratings at the beginning of camp, so these children had less change in their scores from the begin- ning to the end of camp. This suggests that perhaps it is not just CD but also the restrictions of a GFD that shape children’s perceptions of their disease and their quality of life and that, over
abdominal pain, bloating and altered bowel habit, the most often reported extra-intestinal symptoms being fatigue, headache, joint or bone pain, mood disorders and skin manifestations [2,45] . Due to the similarities in clinical outcomes and the absence of diagnostic biomarkers, it is challenging to differ- entiate NCGS from other gluten related disorders. Typically the diagnosis of NCGS is made after the exclusion of celiacdisease and wheat allergy by means of negative celiac serology, negative histological ﬁndings and negative testing for speciﬁc immunoglobulin E (IgE). The diagnosis is further conﬁrmed by a positive oral gluten challenge after exclusion of gluten from the diet for few weeks. The gluten challenge should be implemented in a blinded fashion in order to avoid a possible placebo effect commonly seen in the dietary interventions  . However, this approach lacks speci ﬁcity and is difﬁcult to carry out in clinical practise. In addition, the exclusion of irritable bowel syndrome (IBS) should be considered during the diagnostic process, since gluten may exacerbate the symptoms in these patients
Celiacdisease (CD) is an autoimmune disorder, triggered by gluten and related prolamins in genetically susceptible individuals 1 . CD primarily affects the proximal small intestine, where it progressively leads to villous atrophy. The cornerstone of treatment for CD is a gluten‐freediet (GFD), which excludes wheat, barley and rye 2 . This diet enables CD patients to control their symptoms and avoid intestinal and extraintestinal complications, including osteoporosis with associated increased risk of bone fractures, and development of certain types of cancer 3 . Celiac patients react adversely if they consume gluten, which is the storage group of proteins in certain cereal grains. The protein fractions considered to be the constituents of most concern in celiac patients include the alcohol-soluble fractions (prolamins) of wheat (gliadins), rye (secalins) and barley (hordeins) 4 . The prolamine fraction in oats (avenins) is structurally different from other prolamin fractions, and represents only a small proportion of total oats protein 5 .
sensitivity to dietary gluten in genetically predisposed individuals. The diagnosis of celiacdisease is based on characteristic histological alterations of the small bowel mucosa during gluten consumption and clear clinical remission on avoidance of gluten. The treatment of celiacdisease consists of a life-long, gluten-freediet to heal the duodenal mucosa, improve symptoms and protect from development of complications. The aims of this thesis were to measure some of the environmental factors (e.g. breastfeeding and gluten introduction) considered to play a role in the prevention of celiacdisease and in the development of oral tolerance. Furthermore, to explore the relationship of celiac patients with gluten and the gluten-freediet at different ages, their ability to develop gluten tolerance and the impact of the gluten-freediet on health-related quality of life. Breastfeeding has been shown to prevent, or at least delay the development of celiacdisease. Breast milk contains many immunologic factors that stimulate the infant’s immune system, but its exact role in the prevention of celiacdisease is not known. Furthermore, breast milk contains small amounts of food antigens, like gluten peptides that may contribute to tolerance induction. In chapter 2 we describe the results of a study on the presence of T cell stimulatory epitopes originating from dietary gluten in the breast milk of 23 mothers on a normal diet and of 13 mothers on a gluten-freediet. T cell stimulatory epitopes of both gliadin and glutenin were detected in breast milk but no correlation with the gluten intake of the mother was found. We conclude that infants are exposed to small levels of gluten through breast milk. These small levels may be one of the factors responsible for the induction of oral tolerance to gluten.
symptoms in adults with celiacdisease, before or after the introduction of a gluten-freediet and food restric- tion [7-11]. Children with celiacdisease can also suffer from neurological and psychological disorders, including headaches, attention-deficit/hyperactivity disorder (ADHD), learning and tic disorders, depression and anxiety, mostly before any dietary treatment [12-15]. An association between autism and CD has also been reported, although a direct link still has to be deter- mined [16,17]. Recently, another study suggested the existence of a low prevalence of neurological and psy- chiatric disorders such as febrile seizures, epilepsy, head- ache, mental retardation, neuropathy, and bipolar disorder in children with gluten sensitivity .
Coeliac Disease (CD) is a permanent gluten intolerance, whose pathogenesis involves multiple factors including genetics and environment. CD has different representa- tions and non-specific symptoms such as diarrhea, bloating, pain, flatulence and constipation may sometimes be misleading. Once diagnosed of CD, patients must adhere to GlutenFreeDiet, which consists in the lifelong avoidance of gluten containing foods and of those naturally glutenfree but at risk of contamination. This dietary approach is considered the only therapy in order to avoid symptoms exacer- bation and to reduce the digestive mucosa inflammation, which has been related to higher risks of lymphoproliferative malignancy and other immunological disorders. However, being on a GlutenFreeDiet is not as resolving as it may seem since it has several criticalities. First of all, excluding gluten means limiting food variety so that coeliac patients may have unbalanced intake of several nutrients and develop clinical or subclinical deficiencies. This can be due to scarce attention to qualitative and quantitative composition of diets and poor information about gluten-containing foods, which only patient-tailored dietetic protocol and long-term follow-up can achieve. Secondly, GlutenFreeDiet may not result in complete remission of mucosal damage or in resolution of symptoms. Unintentional contamination of gluten or poor adherence to diet are the main culprits of the incomplete mucosal healing but other triggers may be involved. Recent research has focused on the role of FOD- MAPs in changing gut microbiota and on the improvement of Irritable Bowel Syn- drome (IBS) symptoms after their dietary avoidance or reduction. Since CD and IBS may share many clinical presentations, further studies are needed to evaluate if a subgroup of CD patients whose symptoms are not improved by GlutenFreeDiet could benefit from a new therapeutic approach consisting in both gluten/wheat and FODMAPs avoidance.
Americans are becoming increasingly aware of what they are consuming through their diets. Recently, a large number of people have been removing gluten from their diet in an attempt to alleviate a wide variety of intolerance or allergy-like symptoms (Reilly, 2016). However, not all of these consumers are making educated choices when it comes to removing dietary gluten. One study found that many people who were opting for gluten-free alternative foods were buying these products because they thought it would be healthier, improve overall digestive health, aid in weight loss, or, least likely, they had a gluten sensitivity (Gaesser & Siddhartha, 2012; Reilly, 2016). However, this careless adoption of the glutenfreediet (GFD) is irresponsible due to the nutritional deficiencies that can accompany the diet. Gluten has been condemned as evil by many who are not educated in the characteristics of the molecule. Gluten itself is not unhealthy, toxic, or bad for those who do not have Celiacdisease (CD) or non-celiacgluten sensitivity (NCGS) (Reilly, 2016). Gluten is a general name for a class of alcohol-soluble proteins present in wheat, barley, and rye (Biesiekierski, 2017). This class of proteins contains gliadin and glutenin, which are both characterized by high levels of glutamine and proline amino acids. Although this renders the protein difficult to digest, adverse immune reactions because of this are only observed in patients with CD and NCGS (Biesiekierski, 2017).
When CD is diagnosed, there is usually the assumption that gastrointestinal symptoms will resolve once gluten is eliminated from the diet. Instead, it has been demonstrated that some celiac patients carry on suffering of gastrointestinal symptoms one year after diagnosis even with their correct adherence to GFD and normalization of serum tTG levels [ 9 ]. Such a finding also includes the fact that celiac patients do not report great quality-of-life scores as compared to those of the healthy population [ 41 ]. Therefore, the hypothesis that only mucosal inflammation may have a sensitizing effect or predispose to IBS-type symptoms is not the only way to run. The diet can play a pivotal role in the induction of IBS symptoms [ 42 ] especially FODMAP [ 43 ]. IBS is a common syndrome characterized by abdominal discomfort or pain and is associated with altered bowel habits [ 14 ]. Currently, once major organic gastrointestinal disorders have been excluded, specialists focus on the possible link between an “IBS” clinical picture and molecules such as α-amylase/trypsin inhibitors (resistance molecules contained in cereals to fend off pests and parasites) or dietary habits such as the intake of lactose, dietary nickel, poorly absorbed, and short-chain carbohydrates (i.e., FODMAP). FODMAP are contained in different types of cereals such as wheat, barley, rye, and derived products and sweets and sweeteners such as honey, saccharin, and fructose. There are two other categories that contain high levels of FODMAP including several types of fruits/dried fruit (such as apple, apricot, peach, pear, watermelon, and plum) and vegetables (such as artichoke, asparagus, cauliflower, onion, garlic, and beans). In addition, dairy products are given attention for their high FODMAP content (lactose): milk, yogurt, fresh cheese, semi-aged cheese, and aged cheese. At present, no data is available about FODMAP intake in CD patients [ 44 , 45 ].
Methods: All subjects showed villous atrophy in duodenal biopsies, were HLA-DQ2/DQ8-positive, and fulfilled the Rome III and ACR 1990 criteria respectively for IBS and FMS classification. GFD effectiveness was assessed at baseline and after 1 year, examining the score changes in the Tender Points (TPs) test, Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), Short Form Health Survey (SF-36), Visual Analogue Scales (VAS) for gastrointestinal complaints, pain and tiredness, drug prescriptions and tissue-Trans-Glutaminase (tTG) serum levels. Results: At baseline, all patients had poor Quality of Life and VAS scores, a high number of TPs and drug
Methods: This prospective, observational, hospital-based study was conducted at MTC of tertiary care medical college hospital of southern Rajasthan from Dec. 2017 to Nov. 2018. Total 110 children with SAM were enrolled and screened for celiacdisease on the basis of tissue tTg-IgA/IgG serology. Seropositive cases were kept on glutenfreediet for short period of time and observed for the resolution of symptoms and improvement in growth, monitored by anthropometry on discharge and follow up visit.
In the second instance, it is common for joint pain to be due to another cause, such as arthritis, rather than celiacdisease, in which case changing the diet won’t help alleviate the symptoms. Likewise, people with irritable bowel syndrome (IBS) will have symptoms that persist on a gluten-freediet, which is an indication that the symptoms may not be due to celiacdisease. Thus, an accurate search for alternative causes for the symptoms must be performed. Finally, there are health issues that originate because of celiacdisease but do not resolve on a gluten-freediet. For instance, some patients with peripheral neuropathy will continue to have problems even when on a gluten-freediet. From a practical standpoint, you need to first make sure that the diet is completely gluten-free; then ask your doctor if your symptoms could be due to other causes and have him or her address them appropriately. Only at that point, after a negative search, may you conclude that your symptoms are due to celiacdisease, which unfortunately may persist, so have your doctor treat them appropriately.
Richard Logan developed the concept of the 'coeliac disease iceberg' in 1991 to highlight the fact that for every diagnosed case of CD, many cases remain undetected (World Gastroenterology Organisation, 2007; West et al., 2007). Despite the recent increase in diagnosed cases, evidence suggests that 75-90% of the coeliac population remains undetected in Western countries and mass-screening has been advocated by some researchers (Kaukinen et al., 2010). Poor detection of CD may be due to misdiagnosis (CD symptoms are often indistinguishable from irritable bowel syndrome (IBS) symptoms) or because CD is often asymptomatic (Fasano & Catassi, 2001). Although mass-screening could reduce or eliminate the 'clinical iceberg', it could result in reduced QoL as a result of the drastic changes patients are required to make following diagnosis (Collin, 2005; Paavola et al., 2012).
Gluten sensitivity/intolerance affects about 6 to 7 percent of the population in the United States (Fasano 2012). Gluten is a complex protein found predominantly in wheat (gliadin and glutenin), rye (secalin), barley (hordein) and oats (avenin), which are jointly referred to as prolamins (Biesiekierski 2017). While it is critical for people affected by gluten sensitivity to avoid wheat, rye and barley, some can safely consume oats (Garsed and Scott 2006). This is because the content of prolamin, the protein responsible for the sensitivity, in wheat, barley and rye is much higher—around 40 percent—than that in oats, approximately 15 percent (Haboubi et al. 2006). Eliminating gluten from their diets is critical for people suffering from autoimmune disorders like CeliacDisease (also known as celiac sprue or gluten-sensitive enteropathy) and Wheat Allergy. Non-CeliacGluten Sensitivity (NCGS) is yet another type of gluten intolerance which has recently acknowledged by researchers and is suggested to be the most common gluten-related disorder (Barbaro et al. 2018, Niland and Cash 2018). Contrary to CeliacDisease, which can be diagnosed by medical professionals, the lack of a specific diagnostic procedure for NCGS means that most individuals with NCGS are self-diagnosed (Biesiekierski 2014). The incidence of self-diagnosis of CeliacDisease has increased among people in recent years
An enduring conundrum regarding research into factors associated with gluten-freediet adher- ence in coeliac disease lies in establishing causality. While the present study presents a cogent model for predicting variance in the emotional experience of coeliac disease and gluten-freediet adherence, the correlational design limits the capacity to establish causality. The dynamic interplay of psychological and gastrointestinal symptoms associated with treatment non-adherence suggests these relationships may be most meaningfully interpreted as bi-directional. For example, it could also be the case that the experience of depression/anxiety in ﬂ uences an individual ’ s perceptions of their illness rather than that an individual ’ s perceptions of illness in ﬂ uences experiences of depression or anxiety. The directions of these associations need to be further tested using prospec- tive or interventional research designs. In addition, in the context of the present study, structural equation modelling may have provided a greater capacity to explore the relationships between vari- ables in both directions. Unfortunately, the present study lacked suf ﬁ cient sample size to make this method of analysis viable. Future research should thus focus on recruiting more broadly, to both achieve a higher number of participants to facilitate more complex analyses and a more represen- tative sample. However, it will remain important to ensure that participants are all genuinely diag- nosed with coeliac disease to ensure the validity of ﬁ ndings.
There is a remarkable variation when gluten-containing cereals is ﬁ rst introduced into the infants diet as well as marked differences in risk of developing CDA and CD between participating countries in TEDDY. However, time to ﬁ rst introduction of gluten is not an independent risk factor for developing CD by 5 years of age, neither on an overall level nor on a country level comparison. We speculate that the increased risk of CD among Swedish children compared with children from other countries could be caused by a higher intake of gluten-containing cereals at time of weaning, although this assumption needs to be explored in future studies.
The dietary quality of the GFD will be assessed through food records and interviews. The literature reports that GF equivalents tend to be lower in micronutrients and fibre, but higher in calories, fat and sodium [5, 13]. The participant’s diets will be evaluated for deficiencies and imbalances of macronutrients and micronutrients. We will assess the quantity and quality of carbohydrate intake using the glycemic index as well as glycemic load and calculate dietary gluten in our subject population. Dietary gluten quantification was previously demonstrated in Europe and applied to one of our smaller pilot studies with some limi- tations inherent to methodology and with the Canadian and American nutrient databases. We have described a method to help apply the Osborne calculation in North America  and plan to correlate adherence to gluten consumption and describe our population’s consumption patterns as it relates to CD and T1D.
According to the NASPGHAN Clinical Practice Guidelines Summary for CD, within a pediatric prac- tice of 1,500 children there are probably between five and 20 children with CD, either diagnosed or undiag- nosed (1). As the number of patients with CD increases, it is important to continue making progress in the research, knowledge, and treatment options for CD. Diagnosis of the disease is only the beginning, as the practitioner must provide the education and sup- port for life-long compliance to the GFD. The new food labeling law, the Food Allergen Labeling and Protection Act, has improved our knowledge about the source of many ingredients. The GF food industry has expanded tremendously to provide many new GF products including chicken nuggets, instant chocolate cake, and cereals that are appealing to children (Table 11). Lastly, frequent follow-up by medical profession- als and participation in educational activities and sup- port groups will not only encourage compliance and prevent future complications of untreated CD, but will also improve quality of life. ■