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.

Non-celiac gluten sensitivity is characterised by the presence of gastrointestinal and extraintestinal symptoms following gluten ingestion. Recent studies suggested an association between non-celiac gluten sensitivity and the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). This systematic review aimed to examine literature evidence on the relationship between non-celiac gluten sensitivity and FODMAP intake. A comprehensive search was carried out for randomised clinical trials addressing gastrointestinal symptoms as the primary outcome, published between 2010 and 2020 in Portuguese, English or Spanish, and indexed in Scopus, PubMed, SciELO, Cochrane Library, CINAHL, Embase or VHL (LILACS) databases. The systematic review was performed using the population, intervention, comparison and outcome (PICO) framework. A total of 1133 articles were retrieved for further assessment. Three articles were selected for systematic review, one of which included two interventions with different periods and assessments. Quality of evidence was assessed according to the GRADE protocol. The selected articles used different instruments to measure gastrointestinal symptoms and quality of life, hindering comparison of data. Clinical trials identified an association between decreased gastrointestinal symptoms and FODMAP restriction. There are few studies on the topic, and those available used different instruments to assess gastrointestinal symptoms and quality of life. Nevertheless, current evidence supports the gluten-free diet still represents first-line therapy. However, a FODMAP restriction can decrease gastrointestinal symptoms in individuals with non-celiac gluten sensitivity. Further research is needed to confirm this finding.

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.

This research seeks to determine effects of rising interest in gluten-free foods on U.S. retail food demand and, ultimately, producer and consumer welfare. Increased gluten-free interest led to a modest reduction in cereals and bakery demand and increases in meat, alcoholic beverages, and food away from home demand. Combining estimated effects with an equilibrium displacement model suggests the reduction in cereal and bakery demand decreases wheat and barley producer profits by US$7.2 million/year. After accounting for positive demand impacts on other products, results indicate wheat and barley supply is redistributed away from food production into animal production, increasing wheat producer welfare.

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.

Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and β-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.

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.

Complex, diverse and rarely appearing without comorbidity, the autism spectrum disorders continue to be a source of research interest. With core symptoms variably impacting on social communication skills, the traditional focus of many research efforts has centred on the brain and how genetic and environmental processes impact on brain structure, function and/or connectivity to account for various behavioural presentations. Alongside emerging ideas on autistic traits being present in various clinical states, the autisms, and the overrepresentation of several comorbid conditions impacting on quality of life, other research avenues have opened up. The central role of the brain in relation to autism may be at least partially influenced by the functions of other organs. The gastrointestinal (GI) tract represents an important biological system pertinent to at least some autism. The notion of a gut–brain–behaviour axis has garnered support from various findings: an overrepresentation of functional and pathological bowel states, bowel and behavioural findings showing bidirectional associations, a possible relationship between diet, GI function and autism and recently, greater focus on aspects of the GI tract such as the collected gut microbiota in relation to autism. Gaps remain in our knowledge of the functions of the GI tract linked to autism, specifically regarding mechanisms of action onward to behavioural presentation. Set however within the context of diversity in the presentation of autism, science appears to be moving towards defining important GI-related autism phenotypes with the possibility of promising dietary and other related intervention options onward to improving quality of life.

Whole-grain rye foods reduce appetite, insulin and sometimes glucose responses. Increased gut fermentation and plant protein may mediate the effect. The aims of the present study were to investigate whether the appetite-suppressing effects of whole-grain rye porridge could be enhanced by replacing part of the rye with fermented dietary fibre and plant protein, and to explore the role of gut fermentation on appetite and metabolic responses over 8 h. We conducted a randomised, cross-over study using two rye porridges (40 and 55 g), three 40-g rye porridges with addition of inulin:gluten (9:3; 6:6; 3:9 g) and a refined wheat bread control (55 g), served as part of complete breakfasts. A standardised lunch and an ad libitum dinner were served 4 and 8 h later, respectively. Appetite, breath hydrogen and methane, glucose, insulin and glucagon-like peptide-1 (GLP-1) responses were measured over 8 h. Twenty-one healthy men and women, aged 23–60 years, with BMI of 21–33 kg/m2 participated in this study. Before lunch, the 55-g rye porridges lowered hunger by 20 % and desire to eat by 22 % and increased fullness by 29 % compared with wheat bread (P<0·05). Breath hydrogen increased proportionally to dietary fibre content (P<0·05). Plasma glucose after lunch was 6 % lower after the 55-g rye porridges compared with wheat bread (P<0·05) and correlated to breath hydrogen (P<0·001). No differences were observed in ad libitum food intake, insulin or GLP-1. We conclude that no further increase in satiety was observed when replacing part of the rye with inulin and gluten compared with plain rye porridges.

In mammals, short photoperiod is associated with high depression- and anxiety-like behaviours with low levels of the brain serotonin and its precursor tryptophan (Trp). Because the brain Trp levels are regulated by its ratio to large neutral amino acids (Trp:LNAA) in circulation, this study elucidated whether diets of various protein sources that contain different Trp:LNAA affect depression- and anxiety-like behaviours in C57BL/6J mice under short-day conditions (SD). In the control mice on a casein diet, time spent in the central area in the open field test (OFT) was lower in the mice under SD than in those under long-day conditions (LD), indicating that SD exposure induces anxiety-like behaviour. The SD-induced anxiety-like behaviour was countered by an α-lactalbumin diet given under SD. In the mice that were on a gluten diet before transition to SD, the time spent in the central area in the OFT under SD was higher than that in the SD control mice. Alternatively, mice that ingested soya protein before the transition to SD had lower immobility in the forced swim test, a depression-like behaviour, compared with the SD control. Analysis of Trp:LNAA revealed lower Trp:LNAA in the SD control compared with the LD control, which was counteracted by an α-lactalbumin diet under SD. Furthermore, mice on gluten or soya protein diets before transition to SD exhibited high Trp:LNAA levels in plasma under SD. In conclusion, ingestion of specific proteins at different times relative to photoperiodic transition may modulate anxiety- and/or depression-like behaviours, partially through changes in plasma Trp:LNAA.

Despite tremendous growth in the consumption of gluten-free (GF) foods, there is a lack of evaluation of their nutritional profile and how they compare with non-GF foods. The present study evaluated the nutritional quality of GF and non-GF foods in core food groups, and a wide range of discretionary products in Australian supermarkets. Nutritional information on the Nutrition Information Panel was systematically obtained from all packaged foods at four large supermarkets in Sydney, Australia in 2013. Food products were classified as GF if a GF declaration appeared anywhere on the product packaging, or non-GF if they contained gluten, wheat, rye, triticale, barley, oats or spelt. The primary outcome was the ‘Health Star Rating’ (HSR: lowest score 0·5; optimal score 5), a nutrient profiling scheme endorsed by the Australian Government. Differences in the content of individual nutrients were explored in secondary analyses. A total of 3213 food products across ten food categories were included. On average, GF plain dry pasta scored nearly 0·5 stars less (P< 0·001) compared with non-GF products; however, there were no significant differences in the mean HSR for breads or ready-to-eat breakfast cereals (P≥ 0·42 for both). Relative to non-GF foods, GF products had consistently lower average protein content across all the three core food groups, in particular for pasta and breads (52 and 32 % less, P< 0·001 for both). A substantial proportion of foods in discretionary categories carried GF labels (e.g. 87 % of processed meats), and the average HSR of GF discretionary foods were not systematically superior to those of non-GF products. The consumption of GF products is unlikely to confer health benefits, unless there is clear evidence of gluten intolerance.

Mankind has existed for 2·5 million years but only in the last 10 000 years have we been exposed to wheat. Wheat was first cultivated in the Fertile Crescent (South Western Asia) with a farming expansion that lasted from about 9000BC to 4000BC. Thus it could be considered that wheat (and gluten) is a novel introduction to man'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 5-fold. Perhaps as a result the epidemiology of coeliac disease (CD) or gluten sensitive enteropathy has changed. 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 treatment is a strict lifelong gluten-free diet. However, there is a growing body of evidence to show that a far greater proportion of individuals without coeliac disease are taking a gluten-free diet of their own volition. This clinical entity has been termed non-coeliac gluten sensitivity (NCGS), although the condition is fraught with complexities due to overlap with other gluten-based constituents that can also trigger similar clinical symptoms. This review will explore the relationship between gluten, the rising prevalence of modern coeliac disease, and the new entity of NCGS along with its associated uncertainties.

Autism spectrum disorders represent a diverse and heterogeneous array of conditions unified by the variable presence of specific behaviours impacting social and communicative functions (social affect) alongside other presentation. Common overt characteristics may come about as a consequence of several different genetic and biological processes differentially manifesting across different people or groups. The concept of plural ‘autisms’ is evolving, strengthened by an increasingly important evidence base detailing different developmental trajectories across the autism spectrum and the appearance of comorbidity variably interacting with core symptoms and onwards influencing quality of life. Reports that dietary intervention, specifically the removal of foods containing gluten and/or casein from the diet, may impact on the presentation of autism for some, complement this plural view of autism. Evidence suggestive of differing responses to the use of a gluten- and casein-free diet, defined as best- and non-response, has combined with some progress on determining the underlying genetic and biological correlates potentially related to such dietary elements. The preliminary suggestion of a possible diet-related autism phenotype is the result. This review will highlight several pertinent aspects onwards to an effect of food in some cases of autism including research on the pharmacological activity of food metabolites, immune response, issues with gut barrier function and some contribution from the gut microbiota. These represent promising areas in need of far greater research inspection in order to potentially define such a diet-related subgroup on the autism spectrum.

Coeliac disease (CD) affects about 1 % of the general population. Information concerning gluten intake in the general population is scarce. In particular, variation in gluten intake during the complementary feeding period may be an independent risk factor in CD pathogenesis. We determined the intake of gluten from wheat, barley, rye and oats in a cross-sectional National Danish Survey of Dietary Habits among Infants and Young Children (2006–2007). The study population comprised a random sample of 1743 children aged 6–36 months, recruited from the National Danish Civil Registry. The protein contents from wheat, rye, barley and oats were found in the National Danish Food Composition Table, and multiplied with the amounts in the recipes. The amounts of gluten were calculated as the amount of cereal protein × 0·80 for wheat and oats, ×0·65 for rye and ×0·50 for barley. Dietary intake was recorded daily for seven consecutive days in pre-coded food records supplemented with open-answer possibilities. Gluten intake increased with age (P < 0·0001). Oats were introduced first, rapidly outpaced by wheat, the intake of which continued to increase with age, whereas oats started to decrease at 12 months. Boys had a higher intake of energy (P ≤ 0·0001) and all types of gluten, except for barley (P ≤ 0·87). In 8–10-month-old (P < 0·0001) and 10–12-month-old (P = 0·007), but not in 6–8-month-old infants (P = 0·331), non-breast-fed infants had higher total gluten intake than partially breast-fed infants. In conclusion, this study presents representative population-based data on gluten intake in Danish infants and young children.

Coeliac disease is a lifelong intolerance to the gluten found in wheat, barley and rye, and some patients are also sensitive to oats. The disease is genetically determined, with 10% of the first-degree relatives affected and 75% of monozygotic twins being concordant. Of the patients with coeliac disease 95% are human leucocyte antigen (HLA)-DQ2 or HLA-DQ8 positive. Characteristically, the jejunal mucosa becomes damaged by a T-cell-mediated autoimmune response that is thought to be initiated by a 33-mer peptide fragment in A2 gliadin, and patients with this disorder have raised levels of anti-endomysium and tissue transglutaminase antibodies in their blood. Coeliac disease is the major diagnosable food intolerance and, with the advent of a simple blood test for case finding, prevalence rates are thought to be approximately 1:100. Classically, the condition presented with malabsorption and failure to thrive in infancy, but this picture has now been overtaken by the much more common presentation in adults, usually with non-specific symptoms such as tiredness and anaemia, disturbance in bowel habit or following low-impact bone fractures. Small intestinal biopsy is necessary for diagnosis and shows a characteristically flat appearance with crypt hypoplasia and infiltration of the epithelium with lymphocytes. Diet is the key to management and a gluten-free diet effectively cures the condition. However, this commitment is lifelong and many aisles in the supermarket are effectively closed to individuals with coeliac disease. Compliance can be monitored by measuring antibodies in blood, which revert to negative after 6–9 months. Patients with minor symptoms, who are found incidentally to have coeliac disease, often ask whether it is necessary to adhere to the diet. Current advice is that dietary adherence is necessary to avoid the long-term complications, which are, principally, osteoporosis and small bowel lymphoma. However, risk of these complications diminishes very considerably in patients who are on a gluten-free diet.

We studied dietary risk factors by analysing a questionnaire administered at birth, 1 year and 2½ years of age, as well as the level of glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A), in 7208 2½-year-old children from the All Babies in Southeast Sweden cohort, using the 95th percentile cut-off for autoantibodies to identify children at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate analysis, male gender and maternal coeliac disease implied a risk of possessing IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age of 1 year and a late introduction of gluten were associated with a risk of GADA. Early cessation of breast-feeding (≤2 months of age) was associated with a risk of the simultaneous occurrence of both IA-2A and GADA. In logistic regression analysis, a high consumption of milk at the age of 1 year (odds ratio 2·6) represented a risk for GADA, and maternal coeliac disease (odds ratio 2·9) represented a risk for IA-2A. The combination of an early introduction of cows milk formula and a late introduction of gluten-containing food gave an odds ratio of 6·0 for positivity for at least one autoantibody at 1 and 2½ years of age. The induction of autoantibodies by the age of 2½ years has a male preponderance and is more common in children with maternal type 2 diabetes or maternal coeliac disease. Dietary risk factors for the induction of β-cell autoantibodies in 2½-year-old children are a short duration of breast-feeding, an early introduction of cows milk formula and a late introduction of gluten, as well as a high consumption of milk at the age of 1 year.

We suggested that food preference depends on the interplay between flavour and post-ingestive effects, and we predicted that protein-restricted lambs would acquire preferences for foods paired with supplemental sources of N, including urea (Expts 1 and 2), casein (Expt 3), and gluten (Expt 4). In each experiment, twenty lambs, in two groups of ten, were conditioned as follows: on odd-numbered days, lambs in group 1 received wheat straw (Expts 1, 3, and 4) or ground barley (Expt 2) flavoured with a distinctive flavour, and lambs in group 2 received the same food but with a different flavour. On even-numbered days, flavours were switched and lambs received capsules containing different amounts of urea (ranging from 0.12 to 0.92 g N/d), casein (ranging from 0.23 to 0.69 g N/d), or gluten (ranging from 0.23 to 0.69 g N/d). After conditioning periods of 8 d, lambs were given a two-choice test to determine preference for flavours paired with N. In Expts 1 and 2, lambs preferred the flavours conditioned with urea at lower doses (0.12 g N/d in Expt 1. 0.23 and 0.46 g N/d in Expt 2), but they avoided the flavour associated with urea at the highest dose (0.23 g N/d in Expt 1 and 0.92 g N/d in Expt 2). In Expts 3 and 4, lambs avoided the flavours associated with the lowest doses of casein or gluten (0.23 g N/d), but they preferred the flavours paired with casein or gluten at higher doses (0.46 and 0.69 g N/d). After conditioning, N administrations were suspended and lambs in Expts 3 and 4 were offered a choice of the two flavours at weekly intervals for 2 weeks (extinction); preferences persisted during extinction. Collectively, these results suggest that the post-ingestive effects of N in different forms and concentrations influenced the development of food preferences by lambs.