Probiotics Supplements Reduce ER Stress and Gut Inflammation Associated with Gliadin Intake in a Mouse Model of Gluten Sensitivity.

Exposure to gluten, a protein present in wheat rye and barley, is the major inducer for human Celiac Disease (CD), a chronic autoimmune enteropathy. CD occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, a gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several studies have shown that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD through the modulation of intestinal permeability and the regulation of the immune system. Here, we show that gliadin induces a chronic endoplasmic reticulum (ER) stress condition in the small intestine of a gluten-sensitive mouse model and that the coadministration of probiotics efficiently attenuates both the unfolded protein response (UPR) and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, probiotics administration might potentially represent a new valuable strategy to treat gluten-sensitive patients, such as those affected by CD.

Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies.

Although celiac disease (CD) is an autoimmune disease that primarily involves the intestinal tract, mounting evidence suggests that a sizeable number of patients exhibit neurological deficits. About 40% of the celiac patients with neurological manifestations have circulating antibodies against neural tissue transglutaminase-6 (tTG6). While early diagnosis and strict adherence to a gluten-free diet (GFD) have been recommended to prevent neurological dysfunction, better therapeutic strategies are needed to improve the overall quality of life. Dysregulation of the microbiota-gut-brain axis, presence of anti-tTG6 antibodies, and epigenetic mechanisms have been implicated in the pathogenesis. It is also possible that circulating or gut-derived extracellular structures and including biomolecular condensates and extracellular vesicles contribute to disease pathogenesis. There are several avenues for shaping the dysregulated gut homeostasis in individuals with CD, non-celiac gluten sensitivity (NCGS) and/or neurodegeneration. In addition to GFD and probiotics, nutraceuticals, such as phyto and synthetic cannabinoids, represent a new approach that could shape the host microbiome towards better prognostic outcomes. Finally, we provide a data-driven rationale for potential future pre-clinical research involving non-human primates (NHPs) to investigate the effect of nutraceuticals, such as phyto and synthetic cannabinoids, either alone or in combination with GFD to prevent/mitigate dietary gluten-induced neurodegeneration.

Dietary Lectin exclusion: The next big food trend?

Until recently, with the exception of coeliac disease, gastroenterologists have not been particularly interested in the role of diet in the management of gastrointestinal disorders. However, patients have always felt that diet must play a part in their symptoms and, in the absence of any medical interest, have turned to alternative dietary practitioners for help, which can often have no evidence base. Fortunately, with the advent of the FODMAP diet (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) and the realisation that diet can have a profound effect on the microbiome, medical opinion is now changing. Nevertheless, research on the various diets that are now available is often completely lacking. Lectins are carbohydrate binding proteins which are widely distributed in nature and are found in a whole variety of commonly consumed foods. It seems likely that the exclusion of lectins from the diet could become the next "food fashion" for alternative practitioners to promote, especially as there is some evidence to suggest that certain lectins may be harmful to health. It is, therefore, the purpose of this viewpoint to try and stimulate research on the dietary effects of lectins, which is currently minimal, so that we can pre-empt a situation where we are unable to give patients or the public evidence based advice on this topic.

Parental Perception of Dietary Intervention in Juvenile Idiopathic Arthritis.

Objectives: To evaluate the prevalence of special diet adoption in juvenile idiopathic arthritis (JIA) and parental perceptions of efficacy. Design: An online survey was distributed over a year to nearly 20,000 individuals. Results: Responses from 261 parents of patients with JIA were received. One of three (n = 79) had tried special diets, including gluten-free (66%), anti-inflammatory (41%), and lactose-free (25%). Overall, >50% of 79 parents reported that patients had improved pain or joint swelling. Conclusions: Special diets have been trialed by a third of the patients, with over half reporting symptom improvement. A prospective, controlled trial is warranted to test the efficacy of a dietary approach to JIA.

A randomised, double-blind, cross-over trial to evaluate bread, in which gluten has been pre-digested by prolyl endoprotease treatment, in subjects self-reporting benefits of adopting a gluten-free or low-gluten diet.

The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour. Compared with controls, GS subjects had a favourable cardiovascular lipid profile - lower LDL (4·0 (sem 0·3) v. 2·8 (sem 0·2) mmol/l; P=0·008) and LDL:HDL ratio (3·2 (sem 0·4) v. 1·8 (sem 0·2); P=0·005) and modified haematological profile. The majority of the GS subjects followed a low-gluten lifestyle, which helps to reduce the gastrointestinal (GI) symptoms severity. The low-gluten lifestyle does not have any effect on the quality of life, fatigue or mental state of this population. Consumption of normal wheat bread increased GI symptoms in GS subjects compared with their habitual diet. ANPEP lowered the immunogenic gluten in the treated bread by approximately 40 %. However, when compared with the control bread for inducing GI symptoms, no treatment effects were apparent. ANPEP can be applied in the production of bread with taste, texture and appearance comparable with standard bread.

Amylase-Trypsin Inhibitors in Wheat and Other Cereals as Potential Activators of the Effects of Nonceliac Gluten Sensitivity.

Nonceliac gluten sensitivity (NCGS) is a gluten-related gastrointestinal disorder distinct from celiac disease (CD) and gluten allergy that is not easy to diagnose due to the lack of biomarkers. It is characterized by intestinal symptoms and extraintestinal manifestations with the consumption of gluten-containing foods. In contrast to CD, NCGS patients do not present a genetic predisposition or intestinal villi atrophy. Recent studies question the proinflammatory triggering activity of α-gliadin fraction contained in wheat, since it has been demonstrated that the amylase-trypsin inhibitors (ATIs) exert a strong activating effect on the innate immune response. We aimed to analyze the role of ATIs in the activation of innate immunity and in the development of the symptoms characteristic of NCGS. A systematic literature search was made using databases such as MEDLINE, SciELO, Science Direct, and Scopus, with focus on key words such as "amylase-trypsin inhibitors," "wheat," "gluten," and "celiac." Many studies are available on the structure, inhibition mechanism, and immune system effects of ATIs, mainly focused on IgE-mediated reactions. Recently, with the increase of NCGS interest, has increased the literature on the capacity of ATIs contained in wheat to activate the innate immune system. Literature published to date questions the relationship between activation of the innate immune system and gluten in NCGS. ATIs may have acted as interfering contaminant of gluten and appear as potential activator of innate immunity in NCGS patients. In view of their potential impact, more interventional studies are needed to demonstrate the proinflammatory effect of ATIs.

Clinical Features, Etiologic Factors, Associated Disorders, and Treatment of Palmoplantar Pustulosis: The Mayo Clinic Experience, 1996-2013.

OBJECTIVE: To further characterize clinical characteristics, etiologic factors, associated disorders, and treatment of palmoplantar pustulosis (PPP). PATIENTS AND METHODS: We conducted a retrospective review of patients with PPP at Mayo Clinic between January 1, 1996, and December 31, 2013. RESULTS: Of 215 patients with PPP identified, 179 (83%) were female, and the mean age at onset was 45.3 years. Most patients (n=165, 77%) were current or former smokers. At diagnosis, 15 patients (7%) had an anxiety diagnosis and 9 (4%) had an infection. Nineteen cases (9%) were drug induced. Comorbid conditions included thyroid disease in 18 patients (8%), gluten sensitivity in 3 (1%), and type 2 diabetes mellitus in 21 (10%). In all, 194 patients (90%) received topical corticosteroids, 55 (26%) received phototherapy, and 54 (25%) received systemic agents. CONCLUSION: More than three-fourths of the patients in this study had a history of smoking, which is considered a triggering or aggravating factor for PPP. Regarding comorbid conditions, gluten sensitivity and thyroid disease were found less frequently than previously reported in the literature. Treatment regimens and responses in this cohort varied considerably.

Osteoarticular manifestations of celiac disease and non-celiac gluten hypersensitivity.

Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg. The diagnosis is confirmed by positive specific antibody, anti-transglutaminase or anti-endomysium, specific lesions of the small intestine and a response to strict gluten-free diet. The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia. In the absence of risk factor, osteoporosis, in a premenopausal women or in a man less than 55 years, more is if it is severe and refractory to medications, need to rheumatologists on the track of celiac disease in the absence of digestive symptoms. Osteomalacia is related to secondary hypovitaminosis D malabsorption. Supplementation by calcifediol, water-soluble vitamin D, may be indicated. Celiac disease is associated with an autoimmune disease in almost 1/3 of the cases. Knowing these potential associations allows earlier diagnosis in patients whose only manifestation, a concomitant disease. Anemia, chronic fatigue or unexplained polyarthralgia are symptoms associated with celiac disease to look for specific antibodies. The aim of early diagnosis is to prevent the emergence of other systemic disorders and avoid complications such as bone fractures and cancer, especially intestinal lymphoma. Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out, among patients without specific antibodies and without intestinal lesion of celiac disease. This entity is a cause, at least in part, of increasing interest in gluten-free diet in the general population.

The perspective of celiac disease patients on emerging treatment options and non-celiac gluten sensitivity.

BACKGROUND: Non-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients. METHODS: We performed a large patient survey among unselected CeD patients in Switzerland. RESULTS: A total of 1689 patients were analyzed. 57.5% have previously heard of NCGS. 64.5% believe in the existence of this entity. Regarding a potential influence of NCGS on CeD awareness, 31.7% show a positive and 27.5% a negative perception. Patients with prior use of alternative medicine and women more often have heard of and believe in the existence of NCGS vs. those never having used alternative methods and men, respectively (66.9 vs. 56.9%, p=0.001 and 78.5 vs. 69.0%, p=0.001; 60.7 vs. 44.2%, p<0.001 and 71.0 vs. 60.8%, p=0.002). Women and patients ≥30 years more often show a negative attitude towards NCGS (32.2% vs. 24.8%, p=0.024 and 32.2% vs. 24.2%, p=0.018). With regard to emerging treatment options for CeD, 43.3% have previously heard of novel agents, more women than men (46.0 vs. 38.0%, p=0.019). CONCLUSIONS: Perception of and attitude towards NCGS differ depending on sex, age and prior use of alternative medicine. Knowledge of the progress towards emerging treatment options is currently limited.

Nutritional therapy - Facing the gap between coeliac disease and gluten-free food.

The market of gluten-free bakery products is considerably growing since better diagnostic methods allow identifying an increasing number of people suffering coeliac disease and other gluten-related disorders such as dermatitis herpetiformis, gluten ataxia, wheat allergy and non-coeliac gluten sensitivity. The only and safe treatment available nowadays for these types of disorders is to follow a strict and permanent lifelong gluten-free diet. Beside the people needing to follow a gluten-free diet for health reasons, a new segment of consumers has arisen who consume gluten-free products as a lifestyle choice. Among the bakery products, bread is a major staple food consumed daily all over the world. The dough and bread quality characteristics (such as gas retaining ability, mixing tolerance, resistance to stretch and extensibility and crumb structure) are mostly attributed to the presence of gluten. Despite the improved quality of gluten-free breads in the last number of years, most products on the market are still described as low quality product. In addition to the low overall quality of gluten-free products, the nutritional value of a large number of them is quite poor. In this context, this review gives an overview on the consumers, which need to follow a gluten-free diet for health reasons. The trends in this gluten-free bakery segment will also be reviewed based on the current analysis of marketing studies. An overview of the major ingredients used in gluten-free bread products will be given. The choice of the ingredients discussed in this paper is based on a comprehensive study of the leading gluten-free breads available on the market, as well as a detailed study of the scientific literature. The impact of the various ingredients on bread-making process and bread quality is also part of this review. Major emphasis will be placed on the application of sourdough as a means to improve gluten-free bread quality.

Enfermedad celíaca: ¿qué características tienen nuestros pacientes en el momento del diagnóstico? / Celiac disease: what characteristics do our patients have at the time of diagnosis?

Introducción: la enfermedad celíaca es una patología crónica que con frecuencia presenta los primeros síntomas en la edad pediátrica. En los últimos años ha aumentado el número de diagnósticos, a la vez que se ha reducido la edad a la que se realizan estos. Material y métodos: estudio descriptivo de los antecedentes y las características epidemiológicas, clínicas y diagnósticas de 102 pacientes controlados por enfermedad celíaca en un hospital de tercer nivel. Resultados: el 41,4% son varones y el 58,6% mujeres, la mayor parte de etnia caucásica (94,1%). El 9,8% tienen al menos un familiar de primer grado celíaco, y el 6,9% de segundo grado. La edad media al diagnóstico es 42,8 ± 35,9 meses. El 89,2% presentaban algún síntoma al diagnóstico, mientras en el 10,8% restante el diagnóstico se obtuvo en el cribado de celiaquía por presentar otra patología asociada. Síntomas más frecuentes: pérdida de peso (58%), diarrea (52%), hiporexia (40%), distensión abdominal (24%), alteración del carácter (15%), hábito malabsortivo (13%) y dolor abdominal (12%). Estudio serológico: el 95% presentó anticuerpos antitransglutaminasa positivos, el 85,2% antiendomisio positivos, el 88,4% antigliadina IgG positivos. Estudio del sistema de antígenos leucocitarios humanos (HLA): 97% DQ2, 2% DQ8. Se realizó biopsia duodenal al 62,8% (3% Marsh I, 5% Marsh II, 17% Marsh IIa, 17% Marsh IIIb, 58% Marsh IIIc). Conclusiones: el mayor conocimiento de la enfermedad celíaca podría haber influido en la baja edad media al diagnóstico en la muestra. La aplicación de los criterios diagnósticos de la ESPGHAN de 2012 ha permitido diagnosticar a un relevante número de pacientes sin realizar biopsia (AU)

Introduction: celiac disease is a chronic pathology that often presents the first symptoms in childhood. Diagnoses of celiac disease have increased in recent years, while the age of diagnosis has reduced. Methods: 102 patients with celiac disease controlled in a tertiary hospital. Descriptive study of personal history, epidemiology, symptoms and diagnosis. Results: 41.4% were male and 58.6% female, most of Caucasians (94.1%). 9.8% had at least one first-degree relative celiac, and 6.9% in second degree. The average age at diagnosis is 42.8±35.9 months. 89.2% had symptoms at the moment of diagnosis, while the remaining 10.8% was obtained in the diagnosis of celiac disease screening to present other associated pathology. Common symptoms: weight loss (58%), diarrhea (52%), lack of appetite (40%), abdominal distension (24%), alteration of the character (15%), malabsorptive habit (13%) and abdominal pain (12%). Serological study: 95% positive transglutaminase antibodies, 85.2% positive endomysial antibodies, 88.4% positive anti-gliadin IgG antibodies. HLA study: 97% DQ2, DQ8 2%. Duodenal biopsy was performed to 62.8% (3% Marsh I, 5% Marsh II, 17% IIa Marsh, 17% Marsh IIIb, 58% IIIc Marsh). Conclusions: Increased knowledge about celiac disease among general pediatricians may have influenced the low average age at diagnosis in our sample. The application of diagnostic criteria ESPGHAN 2012 have allowed a significant number diagnoses patients without performing a biopsy (AU)

Inulin and fructooligosaccharide affect in vitro calcium uptake and absorption from calcium-enriched gluten-free bread.

Compromised intestinal calcium absorption affecting a deterioration of bone state is a sign of coeliac disease. Experimental calcium-fortified gluten-free bread (GFB) of improved calcium bioavailability could increase calcium content in the diets of coeliac disease patients, allowing them to obtain the amount of calcium they need for therapeutic use. Prebiotics, including inulin-type fructans (IFs) have a beneficial effect on calcium bioavailability. In the present study, the in vitro model composed of the intestinal-like Caco-2 cells and the human intestinal bacteria (Lactobacillus, Enterococcus and Enterobacteriaceae) were used to analyse the effect of inulin and fructooligosaccharide (FOS) of different chain lengths, on calcium uptake and absorption from experimental GFB. Analysed IFs, especially short-chain FOS, significantly (p < 0.05) increased cellular calcium uptake from GFB digest and stimulated the intestinal bacteria applied in the cultures to the intensive synthesis of organic acids. In particular, the concentration of butyric, valeric and lactic acids increased significantly. Similarly, in the calcium absorption experiment, IFs increased the cellular calcium retention but concomitantly reduced its content in basolateral filtrates. The results obtained suggest that the applied IFs affected differentially calcium uptake and absorption from the experimental calcium-enriched GFB, therefore a further study is needed to assess whether these observations made in vitro contribute to IF effects on calcium absorption from experimental GFB in vivo.

Dieta pobre en FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) en el síndrome de intestino irritable: indicación y forma de elaboración / Diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the treatment of irritable bowel syndrome: indications and design

En los últimos años está creciendo el interés en la dieta pobre en fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) como pilar importante en el tratamiento del síndrome de intestino irritable (SII). Este modelo de dieta lo desarrolló un equipo multidisciplinar de la Universidad de Monash, en Melbourne, y empezó a ganar notoriedad a partir de la publicación de un estudio en 2008 que demostraba que los hidratos de carbono fermentables (FODMAPs) de la dieta actuaban como causantes de síntomas en los pacientes con SII. Desde entonces se han llevado a cabo varios ensayos controlados aleatorizados que, aunque con muestras reducidas de pacientes, han vuelto a demostrar las ventajas de este modelo dietético (AU)

In recent years, there has been growing interest in diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) as an important mainstay in the treatment of irritable bowel syndrome (IBS). This model of diet was developed by a multidisciplinary team from the Monash University in Melbourne and became well-known after the publication of a study in 2008 showing that dietary FODMAPs acted as causing factors in patients with IBS. Since then there have been several randomized controlled trials which, although with small sample sizes, have again shown the benefits of this dietary pattern (AU)

[Nutritional Therapy for Children and Adolescents with Autism Spectrum Disorders: What is the Evidence?]. / Ernährungstherapie bei Autismus-Spektrum-Störungen im Kindes- und Jugendalter: wie ist die Evidenz?

BACKGROUND: Autism spectrum disorders (ASDs) are a group of developmental disabilities in childhood and adolescence. Beside genetic predisposition also environmental influences may contribute to the ASD pathogenesis. Family members of children and adolescents with ASD often ask for specific diets to alleviate ASD-associated symptoms. The aim of this review is to provide evidence-based data on nutritional interventions for children and adolescents with ASD, thus enabling practitioners to competently assess these diets. METHODS: Applying defined inclusion and exclusion criteria, a systematic literature research in PubMed, Cinahl and The Cochrane Library was conducted. Studies published earlier than 1999 were excluded. Study quality was assessed by using the CONSORT, STROBE or PRISMA checklist, respectively. RESULTS: 12 randomised controlled studies and 2 non-controlled studies could be included in the evaluation (n=971). There is no proven efficacy of the widely used gluten-free casein-free diets (GFCF), and no respective predictive marker has been proven significant. CONCLUSION: Based on available data, no evidence based recommendations regarding nutritional interventions for children and adolescents with autism spectrum disorders can be made. Future studies need to clarify whether particular patients may yet benefit from certain diets.

Gluten and casein supplementation does not increase symptoms in children with autism spectrum disorder.

AIM: A gluten- and casein-free diet is often given to children with autism spectrum disorder (ASD). We aimed to determine the effect of gluten and casein supplementation on maladaptive behaviour, gastrointestinal symptom severity and intestinal fatty acids binding protein (I-FABP) excretion in children with ASD. METHODS: A randomised, controlled, double-blind trial was performed on 74 children with ASD with severe maladaptive behaviour and increased urinary I-FABP. Subjects were randomised to receive gluten-casein or a placebo for seven days. We evaluated maladaptive behaviour before and after supplementation, using I-FABP excretion, the approach withdrawal problem composite subtest of the Pervasive Developmental Disorder Behavior Inventory and the Gastrointestinal Symptom Severity Index. RESULTS: The mean approach withdrawal problem composite score was significantly higher before supplementation than after, both in the placebo and in the gluten-casein group. However, the mean difference was not significant and may have been caused by additional therapy. There was no significant difference in gastrointestinal symptoms and urinary I-FABP excretion. CONCLUSION: Administrating gluten-casein to children with ASD for one week did not increase maladaptive behaviour, gastrointestinal symptom severity or urinary I-FABP excretion. The effect of prolonged administration or other mechanisms of enterocyte damage in ASD should be explored.

Bones of contention: bone mineral density recovery in celiac disease--a systematic review.

Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.

Celiac disease, non-celiac gluten sensitivity and inflammatory bowel disease.

Celiac disease (CD) and inflammatory bowel disease (IBD), such as Crohn's disease (CrD) and ulcerative colitis (UC), are chronic inflammatory condition of the gastro-intestinal tract. The prevalence of IBD in celiac patients has been reported as 5-10 times higher than in the general population. The possibility of the presence of CD in IBD should be considered in IBD patients with long-term iron deficiency anemia (IDA) not responsive to iron supplementation. Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra intestinal symptoms due to the ingestion of gluten-containing food in subject without CD and/or wheat allergy. Patients with Crohn's disease and SR-NCGS were more significantly affected by joint pains compared to UC patients (50% versus 11.1%). In Crohn's patients, a higher percentage of fatigue (50% versus 38.9%) and headache (27.3% versus 22.2%) was evident. For the association between NCGS and IBD new studies are warranted and, at this moment, a gluten free diet (GFD) may be useful more in CrD than in UC.

Bioavailability of free lysine and protein-bound lysine from casein and fishmeal in juvenile turbot (Psetta maxima).

In the present study, a linear regression analysis between lysine intake and lysine retention was conducted to investigate the efficiency of lysine utilisation (k(Lys)) at marginal lysine intake of either protein-bound or free lysine sources in juvenile turbot (Psetta maxima). For this purpose, nine isonitrogenous and isoenergetic diets were formulated to contain 2·25-4·12 g lysine/100 g crude protein (CP) to ensure that lysine was the first-limiting amino acid in all diets. The basal diet contained 2·25 g lysine/100 g CP. Graded levels of casein (Cas), fishmeal (FM) and L-lysine HCl (Lys) were added to the experimental diets to achieve stepwise lysine increments. A total of 240 fish (initial weight 50·1 g) were hand-fed all the experimental diets once daily until apparent satiation over a period of 56 d. Feed intake was significantly affected by dietary lysine concentration rather than by dietary lysine source. Specific growth rate increased significantly at higher lysine concentrations (P< 0·001). CP, crude lipid and crude ash contents in the whole body were affected by the dietary treatments. The linear regression slope between lysine retention and lysine intake (k(Lys)) was similar between all the dietary lysine sources. The k(Lys) values for the diets supplemented with Cas, Lys or FM were 0·833, 0·857 and 0·684, respectively. The bioavailability of lysine from the respective lysine sources was determined by a slope-ratio approach. The bioavailability of lysine (relative to the reference lysine source Cas) from FM and Lys was 82·1 and 103 %, respectively. Nutrient requirement for maintenance was in the range of 16·7-23·4 mg/kg(0·8) per d, and did not differ between the treatments. There were no significant differences in lysine utilisation efficiency or bioavailability of protein-bound or crystalline lysine from the respective sources observed when lysine was confirmed to be the first-limiting nutrient.

Celiac disease treatment: gluten-free diet and beyond.

The basis for celiac disease (CD) treatment is a strict lifelong gluten-free diet. On the diet, the small intestinal mucosal injury heals and gluten-induced symptoms and signs disappear. The mucosal healing is a prerequisite for sustaining health and is also obtained with a diet containing oats and trace amounts of gluten, industrially purified wheat starch-based gluten-free products. The small intestinal mucosa does not heal in noncompliant people, nor when a patient is inadvertently ingesting gluten. Development of adjunctive or alternative therapies is on its way. There are several novel treatment pipelines within academy and industry. Examples are the ideas of using glutenases as a drug to degrade the ingested gluten, polymers to bind and sequester the gluten to the feces, and also vaccine development for an immunotherapy to induce tolerance towards gluten. Clinical drug trials are to be foreseen in CD, soon also in children.