Congruency of genetic predisposition to lactase persistence and lactose breath test

The physiological decline of lactase production in adulthood, in some individuals, is responsible for the so-called “Lactose Intolerance.” This clinical syndrome presents with gastrointestinal and non-gastrointestinal symptoms following the consumption of dairy containing food. Lactose intolerance can be evaluated by means of the Lactose Breath Test (phenotype) and/or genetic evaluation of lactase-gene polymorphism (genotype). A comparison of the two tests was carried out in a large number of symptomatic adult subjects, which are selected and not representative of the general population. Congruency was as high as 88.6%. Among lactase non-persistent (genotype C/C), 14 subjects showed a negative Lactose Breath Test (LBT), possibly due to young age. Among lactase-persistent (genotype C/T), four subjects showed a positive LBT, which helps to diagnose secondary lactose intolerance. Symptoms, both gastrointestinal and extra-gastrointestinal, were reported by 90% of patients during the breath test. Clinical use of both tests in the same patients could be taken into consideration as a sharp diagnostic tool. We suggest considering the use of the genetic test after LBT administration, when secondary hypolactasia is suspected, for completion of diagnostic procedures

Ultrastructural changes in enterocytes in subjects with Hashimoto's thyroiditis

We have recently described1 mucosal ultrastructural impairments, such as height and thickness of microvilli, space between microvilli, and thickness of tight junctions, in non-coeliac type 1 diabetic patients after a preliminary report of an alteration in intestinal mucosal permeability (IP) evaluated by the lactulose/mannitol (LA/MA) test.2,3 Therefore, in the “aetiological” classification of autoimmunity based on initiating factors,4 the category of diet induced diseases could be expanded to include type 1 diabetes and, perhaps, other endocrine autoimmune diseases. Thyroiditis is the most frequently associated autoimmune endocrine disease with type 1 diabetes. Moreover, type 1 diabetes and Hashimoto thyroiditis present similar pathogenetic mechanisms of cellular damage, a cell mediated autoimmunity induced by Th1 cytokines. However, mucosal intestinal morphology and function have not yet been studied in autoimmune thyroiditis patients. Hence we investigated intestinal mucosal ultrastructural morphology and IP in a group of patients with autoimmune thyroiditis. The study was approved by the local ethics committee. Fourteen patients (12 females and 2 males; mean age 33.2 (SD 10.2) years) and 23 controls (12 females and 11 males; mean age 27.9 (SD 8.01) years) were enrolled into the study after giving written informed consent. The diagnosis of autoimmune thyroiditis was based on the following criteria: plasma autoantibody TPO positive at high titre and a typical thyroiditis ultrasound pattern. All patients were in euthyroidism (normal FT3, FT4, and TSH plasma levels without hormonal therapy). Mean duration of known disease was 5.2 (2.5) years. All patients were negative for the presence of antigliadin antibodies IgA and IgG, antiendomysium antibodies IgA, as well as antihuman transglutaminase IgA following a gluten rich Mediterranean diet. Type 1 diabetes mellitus was excluded according to the 1997 American Diabetes Association criteria, and none of the participants had a family history of diabetes mellitus. Other intestinal and endocrine diseases were excluded through clinical and, when indicated, laboratory evaluation. Food or other allergies were excluded. None of the subjects reported gastrointestinal signs or symptoms, or was a habitual smoker, abuser of alcohol, or regularly took non-steroidal anti-inflammatory drugs

The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update

Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally

Diagnosis of Non-Celiac Gluten Sensitivity (NCGS)

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

<p>Abstract</p> <p>Background</p> <p>Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.</p> <p>Methods</p> <p>CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.</p> <p>Results</p> <p>Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (<it>P </it>= 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (<it>P </it>= 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (<it>P </it>= 0.0124) and IL-21 (<it>P </it>= 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (<it>P </it>= 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (<it>P </it>= 0.0325) and CD patients (<it>P </it>= 0.0293).</p> <p>Conclusions</p> <p>This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.</p

A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objective: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Design: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. Setting: The European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects: Women (n 334 850) from the EPIC study. Results: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, Ptrend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, Ptrend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, Ptrend<0·01). Conclusions: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC

Autism: what is it?

An overview of autism is provided. Hystory, prevalence and causes are described