Acute Appendicitis (AA) is an inflammatory condition of the vermiform appendix in the caecum of the colon. Genetic polymorphisms have been suggested as risk factors predisposing to AA susceptibility but have remained relatively unknown, due to insufficient sample size in previous analyses. Therefore, the primary research aim was to identify genetic variants associated with AA. It was hypothesised that gene polymorphisms associated with AA will provide a connection to other diet-related inflammatory diseases. Genetic variants associated with AA were studied via a Genome-Wide Association Scan (GWAS) using the Global Biobank Meta-Analysis Initiative (GBMI). The GBMI is a collaborative consortium of 23 biobanks with a publicly released repository of de-identified genetic data linked with digital health records spanning 4 continents with a study population size of over 2.2 million consented individuals of multiple ancestral backgrounds1. A linear regression model was used to estimate the association between single nucleotide polymorphisms (SNPs), across the human genome, and AA by each contributing biobank. The results were then meta-analysed with a total of 32,706 cases and 1,075,763 controls. In the present study, the free open-source Complex Traits Genetic Virtual Lab (CTG-VL) platform was used to access, analyse, and visualise the GWAS summary statistics of AA2. Genome-wide significantly associated SNPs (p-value < 5 x 10-8) were further searched for their associations with health-related traits in publicly available GWAS summary statistics. Upon analysis, significantly associated SNPs for AA were identified within or nearby nine genes. HLX, NKX2-3, LTBR, and DLEU1 are genes involved in immune responses; IRF8 associated with maturation of myeloid cells; OSR-1 responsible for transmembrane ion transporter activity; NCALD a regulator of G protein-coupled signal transduction. In addition, based on the hypothesis, the SNP of key clinical importance was the HLA-C rs2524046 (p-value = 2.38 x 10-8), with the AA risk-increasing allele C being also strongly associated with a higher risk of coeliac disease (CD). The CD is an autoimmune condition where gluten, a protein present in grains such as barley, rye, and wheat, elicits an inflammatory response that results in damage to the small intestine lining. Considering how both AA and CD share the same SNP, it is possible to speculate whether gluten initiates a similar pathophysiological mechanism that exacerbates inflammation in the vermiform appendix in AA. In conclusion, the top AA associated SNPs suggests its development could be due to immunological responses influenced by dietary nutrient intake. The HLA-C SNP is common to AA and CD, suggesting that the gluten protein found in certain cereal grains possibly contributes to the pathophysiology of AA like CD. This warrants further investigations into whether dietary gluten could play a key role in AA development.

Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD (n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject β-diversity, P < 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes (Pgroup < 0·001) and class Erysipelotrichia (Pgroup = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline (Pinteraction ≤ 0·009). No differences were found in faecal bacterial α-diversity (Pgroup ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation (Pgroup = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).

Wheat was first cultivated in the Fertile Crescent (South Western Asia) with a farming expansion that lasted from around 9000 BC to 4000 BC. Whilst humans have been exposed to wheat for around the last 10 000 years, humans have existed for greater than 2·5 million years. Therefore, wheat (and thereby gluten) are relatively new introductions to our diet! By the end of the 20th century, global wheat output had expanded by 5-fold, with a corresponding increase in the prevalence of gluten-related disorders. Coeliac disease (CD) is a state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals. CD now affects 1 % or more of all adults, for which the management is a strict lifelong gluten-free diet (GFD). However, there is a growing body of evidence to show that a far greater proportion of individuals without CD are self-initiating a GFD. This includes individuals initiating a GFD as a lifestyle choice, people with irritable bowel-type symptoms and those diagnosed with non-coeliac gluten (or wheat) sensitivity. Despite a greater recognition of gluten-related disorders, gaps still remain in our understanding of both their aetiology and management. This article explores the role of the gluten-free diet in gluten-related disorders, along with current uncertainties.

The gluten-free diet is based on the consumption of foods without gluten, which aims to manage celiac disease. The concern of celiac patients is that these foods should be safe. However, gluten contamination can affect these foods. The objectives of this review and meta-analysis were first, to identify articles that detected gluten contamination in gluten-free foods using validated methods. Second, to quantify the overall prevalence of gluten contamination of naturally gluten-free foods, labelled gluten-free products, and meals prepared in food services. Third, to highlight the influence of the country’s income and the period of study on this prevalence. The studies were identified in Scopus, Science Direct, Web of Science, PubMed, and Google Scholar. Forty articles were included according to PRISMA guidelines. The statistical meta-analysis was performed using MedCalc 19 software. The results show that in the gluten-free foods analysed, the overall prevalence of gluten contamination was estimated at 15.12% (95% CI: 9.56%–21.70%), with more than 20 mg/kg of gluten. Naturally gluten-free foods were significantly more contaminated than labelled gluten-free products and than meals in food services (28.32%; 9.52%; 4.66% respectively; p < 0.001). Moreover, it was noticed that oats were the most contaminated food. In addition, the prevalence of gluten contamination has significantly decreased over time. The majority of the studies were carried out in upper-middle-income and high-income countries, while only one study was conducted in lower-middle income countries. Therefore, it is necessary to implement preventive actions to reduce gluten contamination, ensuring safe gluten-free foods for celiac patients, including low-income countries.

There are currently no universal evidence-based nutrition guidelines that address the gluten-free (GF) diet for children/youth (4–18 years). A GF food guide was created to help children/youth with coeliac disease (CD) and their families navigate the complexities of following a GF diet. Guide formation was based on pre-guide stakeholder consultations and an evaluation of nutrient intake and dietary patterns. The study objective was to conduct an evaluation on guide content, layout, feasibility and dissemination strategies from end-stakeholder users (children/youth with CD, parents/caregivers and health care professionals). This is a cross-sectional study using a multi-method approach of virtual focus groups and an online survey to conduct stakeholder evaluations. Stakeholders included children/youth (4–18 years), their parents/caregivers in the coeliac community (n 273) and health care professionals (n 80) with both paediatric and CD experience from across Canada. Thematic analysis was performed on focus group responses and open-ended survey questions until thematic saturation was achieved. χ2 and Fisher’s exact statistical analyses were performed on demographic and close-ended survey questions. Stakeholders positively perceived the guide for content, layout, feasibility, ethnicity and usability. Stakeholders found the material visually appealing and engaging with belief that it could effectively be used in multi-ethnic community and clinical-based settings. Guide revisions were made in response to stakeholder consultations to improve food selection (e.g. child-friendly foods), language (e.g. clarity) and layout (e.g. organisation). The evaluation by end-stakeholders provided practical and patient-focused feedback on the guide to enable successful uptake in community and clinical-based settings.

The gluten-free (GF) diet is the only treatment for coeliac disease (CD). While the GF diet can be nutritious, increased reliance on processed and packaged GF foods can result in higher fat/sugar and lower micronutrient intake in children with CD. Currently, there are no evidence-based nutrition guidelines that address the GF diet. The objective of this cross-sectional study was to describe the methodological considerations in forming a GF food guide for Canadian children and youth (4–18 years) with CD. Food guide development occurred in three phases: (1) evaluation of nutrient intake and dietary patterns of children on the GF diet, (2) pre-guide stakeholder consultations with 151 health care professionals and 383 community end users and (3) development of 1260 GF diet simulations that addressed cultural preferences and food traditions, diet patterns and diet quality. Stakeholder feedback identified nutrient intake and food literacy as important topics for guide content. Except for vitamin D, the diet simulations met 100 % macronutrient and micronutrient requirements for age–sex. The paediatric GF plate model recommends intake of >50 % fruits and vegetables (FV), <25 % grains and 25 % protein foods with a stronger emphasis on plant-based sources. Vitamin D-fortified fluid milk/unsweetened plant-based alternatives and other rich sources are important to optimise vitamin D intake. The GF food guide can help children consume a nutritiously adequate GF diet and inform policy makers regarding the need for nutrition guidelines in paediatric CD.

Adherence to a gluten-free diet (GFD) is the only available treatment for gluten-related disorders, although a GFD may also be followed for discretionary reasons. The main objectives of the present study were to (1) describe and test for differences in key nutrient intakes among Canadians who follow a GFD compared with Canadians with no dietary exclusions and (2) describe additional dietary avoidances adhered to by Canadians who avoid gluten. We conducted a secondary analysis of the cross-sectional 2015 Canadian Community Health Survey-Nutrition Survey, which included a general health survey and 24-h dietary recall (n 20 487). Participants were categorised as those who avoid dietary gluten and those who reported no avoidances. Key nutrient intakes were assessed, as a percentage of Dietary Recommended Intakes, including fibre, B vitamins, vitamin D, Ca, Fe, Na and Zn, and compared between the two groups using t tests. Canadians who avoided gluten had significantly lower intakes of folate, vitamin B12, vitamin D, Fe, Na and Ca compared with those who did not avoid any food groups. However, Canadians who reported following a GFD were significantly more likely to use vitamin or mineral supplements in the past 30 d. More than 20 % of those who avoided gluten also avoided dairy products. Findings suggest that following a GFD places Canadians at risk for nutrient inadequacies, particularly folate, Ca and vitamin D. Further research is required to further examine how multiple dietary avoidances among those who avoid gluten may contribute to dietary inadequacies.

The rising popular belief that gluten is unhealthy has led to growth in gluten avoidance in people without coeliac disease. Little information is available on their dietary profiles and their dietary behaviours. Our aim was to compare the consumption of organic foods between gluten avoiders and non-avoiders, and their places of food purchase. We described their sociodemographic and dietary profiles. The study population included participants of the NutriNet-Santé cohort who completed both a food exclusion questionnaire and an organic semi-quantitative FFQ (n 23 468). Food intake and organic food consumption ratios were compared using multivariable adjusted ANCOVA models. Associations between gluten avoidance and organic food consumption as well as places of food purchase were investigated with multivariable logistic regression. Participants avoiding gluten were more likely to be women and had a healthier dietary profile. Organic food consumption was higher among gluten avoiders (48·50 % of total diet for total avoiders, 17·38 % for non-avoiders). After adjustments for confounders, organic food consumption and purchase in organic stores were positively associated with gluten avoidance: adjusted OR (aOR)Q5 v.Q1 organic food = 4·95; 95 % CI 3·70, 6·63 and aORorganic stores v.supermarkets = 1·82; 95 % CI 1·42, 2·33 for total avoiders. Our study highlights that individuals avoiding gluten are high organic consumers and frequently purchase their foods in organic stores which propose an extended offer of gluten-free food. Further research is needed to determine the underlying common motivations and the temporality of the dietary behaviours of healthy people avoiding gluten.

This study determined the gluten content of foods and meals consumed by coeliac disease (CD) patients who adhere to a gluten-free diet, and to estimate the total daily intake of gluten of these patients. CD patients fulfilling defined inclusion criteria were preselected and approached for participation in the study. Duplicate portions (DP) of foods and mixed dishes were collected from the CD patients for evaluating complete daily food intake during two individual days. Also, for these days, written food records were completed by the participants. From each DP, a laboratory sample was prepared and analysed for its gluten concentration and total daily gluten intake was calculated. Each individual’s total daily intakes of energy and macronutrients were calculated using the Dutch food composition database. In total, twenty-seven CD patients participated, seven males and twenty females, aged between 21 and 64 years. In thirty-two (6 %) of 499 food samples collected in total, more than 3 mg/kg gluten was present. In four of these thirty-two samples, the gluten concentration was above the European legal limit of 20 mg/kg and three of the four samples had a gluten-free label. The maximal gluten intake was 3·3 mg gluten/d. The gluten tolerance for sensitive CD patients (>0·75 mg/d) was exceeded on at least six out of fifty-four study days. To also protect these sensitive CD patients, legal thresholds should be re-evaluated and the detection limit of analytical methods for gluten analysis lowered.

The only generally accepted treatment of coeliac disease (CD) is a lifelong gluten-free diet. Wheat gluten proteins include gliadins, low and high molecular weight glutenins. However, we have found significant structural variations within these protein families among different cultivars. To determine which structural motifs might be less toxic than others, we assessed five variants of α-gliadin immunodominant CD-toxic peptides synthesised as 16mers in CD T cell stimulation assays with gluten-sensitive T cell lines generated from duodenal biopsies from CD-affected individuals. The peptides harboured the overlapping T cell epitopes DQ 2.5-glia-α-2 and naturally occurring variants that differed in certain amino acids (AA). The results revealed that introduction of two selected AA substitutions in α-gliadin peptides reduced immunogenicity. A peptide with three AA substitutions involving two glutamic acids (E) and one glutamine residue (G) revealed the peptide was negative in 5:5 samples. We used CD small-intestinal organ culture to assess CD toxicity that revealed two peptides with selected substitution of both glutamic acid (E) and proline (P) residues abrogated evidence of CD toxicity.

Follow-up modalities for adult coeliac patients remain controversial. Non-invasive markers to identify coeliac patients on a gluten-free diet (GFD) with persistence of villous atrophy (VA) are still lacking. We aim to develop a score to stratify coeliac patients on a GFD according to their risk of having persistent VA and to tailor follow-up modalities accordingly. The clinical notes of over 700 coeliac patients attending our unit (September 1999–November 2018) were retrospectively examined. A total of 273 patients on a GFD with a histological follow-up performed 12–24 months after diagnosis were selected. We developed a bivariable model based on diet adherence and clinical response evaluated by previously validated methods. A four-level score (0·5, 1·5, 3, 4) was obtained. Patients on a strict GFD and with good clinical conditions (score 4) have a very low risk of persistence of VA (2 (95 % CI 1, 5) %). Conversely, the risk is very high (46 (95 % CI 25, 68) %) in patients with poor adherence to a GFD and unsatisfactory clinical response (score 0·5). A score of 1·5 (poor GFD adherence and persistent well-being) is linked with a high risk (23 (95 % CI 14, 36) %). Risk is intermediate (6 (95 % CI 3, 10) %) in patients scoring 3 (strict GFD and no/partial clinical improvement). Three patients who developed complications belonged to this scenario. Patients at low risk of persistent VA can be followed-up non-invasively, whereas a biopsy should be repeated in those at high/very high risk. Case-by-case evaluation is needed in patients at intermediate risk. Studies on a larger sample size are required to confirm these data.

The number of people avoiding gluten is growing in many Western countries. However, little information is available on their sociodemographic and dietary profiles. We aimed to describe sociodemographic, behavioural and dietary profiles of participants avoiding gluten in the NutriNet-Santé cohort. Participants of the NutriNet-Santé cohort – excluding coeliac patients – who completed a questionnaire about food exclusions, with complete data on sociodemographic characteristics and dietary intake were included (n 20 456). Food group consumptions and nutrient intakes according to self-reported avoidance of gluten were estimated using ANCOVA adjusted for age, sex and daily energy intake. Based on principal component analysis, three dietary patterns (DP) were identified. Association between DP and avoidance of gluten was investigated using multivariate logistic regression. All data were weighted on the French census. A total of 10·31 (95 % CI 9·90, 10·73) % of the participants declared avoiding gluten, of which 1·65 % totally. They were more likely to be women, older persons, non-smokers, to have a lower educational level and declared more food intolerances. They had higher consumption of fruit, vegetables and lower consumption of dairy products, salty/sweet and fatty foods and alcohol. After adjustments on confounders, a healthy dietary pattern was positively associated with total gluten avoidance (ORQuintile5vsQuintile1 = 14·44, 95 % CI 8·62, 24·19). Our study highlighted that, in this population, individuals who avoid gluten from their diet tend to have a diet more favourable to health. These results can serve as a basis for future studies investigating the potential consequences of a gluten-free diet in non-coeliac population.

Although the quantity of gluten that a well-instructed coeliac patient can involuntarily ingest is <10 mg of gluten/d which cannot induce significant villous damage, coeliac patients often attribute the origin of symptoms to the involuntary ingestion of trace quantities of gluten, either certain or hypothetical. Our aim was to evaluate whether the occurrence of symptoms in coeliac patients who histologically responded to a strict gluten-free diet was related to the involuntary consumption of minimal quantities of gluten. A case–control study to assess the association between gluten exposure and the occurrence of symptoms was designed. Between January 2017 and May 2018, coeliac patients attending our outpatient clinic were interviewed to detect the presence of symptoms. Based on a specifically designed form, patients were also divided into different risk groups of gluten exposure. A total of ninety-five coeliac patients on a strict gluten-free diet and with known histological recovery were enroled. Of them, fifty-two of them reported symptoms and they were enroled as cases; the remaining forty-three patients denied symptoms and were enroled as controls. Although this was not statistically significant, gluten exposure was more frequent in controls (Fisher’s exact test, P=0·07). Our results show no relationship between exposure to minimal quantities of gluten and onset of symptoms in coeliac patients. Symptoms are more frequent in patients who have no risk of gluten exposure. It is possible that the presence of these symptoms leads the patients to avoid situations that may place them at risk of gluten exposure.

Coeliac disease (CD) is an autoimmune gastrointestinal disorder whereby the ingestion of gluten, a storage protein found in wheat, barley and rye, causes damage to intestinal mucosa with resultant malabsorption, increased risk of anaemia and osteoporosis. Worldwide estimates suggest 1% of the population have CD. With no cure, the only treatment is a gluten-free diet (GFD). Adhering to a GFD can be very challenging; it requires knowledge, motivation and modified behaviours. Assessing adherence to a GFD is methodologically challenging. This review aims to provide an overview of the literature reporting adherence to a GFD in people with CD and the methodological challenges encountered. From six studies it has been reported that rates of adherence to a GFD range between 45 and 90% in patients of different ethnicities with CD. GF dietary adherence can be influenced by age at diagnosis, coexisting depression, symptoms on ingestion of gluten, nutrition counselling, knowledge of GF foods, understanding of food labels, cost and availability of GF foods, receiving GF foods on prescription and membership of a coeliac society. To date only five intervention studies in adults with CD have been undertaken to improve GF dietary adherence. These have included dietary and psychological counselling, and the use of online training programmes, apps, text messages and telephonic clinics. Future interventions should include people of all ethnicities, consider patient convenience and the cost-effectiveness for the healthcare environment.

Humankind has existed for 2·5 million years but only in the past 10 000 years have we been exposed to wheat. Therefore, it could be considered that wheat (gluten) is a novel introduction to humankind's diet! Prior to 1939, the rationing system had already been devised. This led to an imperative to try to increase agricultural production. Thus, it was agreed in 1941 that there was a need to establish a Nutrition Society. The very roots of the Society were geared towards necessarily increasing the production of wheat. This goal was achieved and by the end of the 20th century, global wheat output had expanded by 5-fold. Perhaps, as a result, the epidemiology of coeliac disease (CD) or gluten sensitive enteropathy has changed. CD now affects 1 % or more of all adults. Despite this, delays in diagnosis are common, for every adult patient diagnosed approximately three–four cases are undetected. This review explores humankind's relationship with gluten, wheat chemistry, the rising prevalence of modern CD and the new entity of non-coeliac gluten or wheat sensitivity. The nutritional interventions of a low fermentable oligo-, di- and mono-saccharides and polyols diet and gluten-free diet (GFD) for irritable bowel syndrome and the evidence to support this approach (including our own published work) are also reviewed. There appears to be a rising interest in the GFD as a ‘lifestyler’, ‘free from’ or ‘clean eater’ choice, causing concern. Restrictive diets may lead to potential nutritional implications, with long-term effects requiring further exploration.

The spectrum of gluten-related disorders includes coeliac disease (CD), wheat allergy (WA) and the suggested entity of non-coeliac gluten sensitivity (NCGS). An increasing number of the world’s population are avoiding gluten due to the assumption of health benefits and self-diagnosed gastrointestinal and/or extra-intestinal symptoms. Unlike CD and WA, NCGS is a relatively new entity with an unknown prevalence and mechanisms, complicated by recent literature suggesting that gluten is not the only food component that may trigger symptoms experienced by this group of patients. The term ‘non-coeliac wheat sensitivity’ has been proposed as a more accurate term, allowing inclusion of other non-gluten wheat components such as fructans and amylase–trypsin inhibitors. There is inconsistent evidence when evaluating the effects of a gluten challenge in patients with suspected NCGS and there is a need for a standardised procedure to confirm the diagnosis, ultimately enabling the optimisation of clinical care. The present review will give an overview of the different gluten-related disorders and discuss the most recent scientific evidence investigating NCGS.