Food Allergy and Intolerance: A Narrative Review on Nutritional Concerns.

Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food-along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.

Food Intolerance of Unknown Origin: Caused by Mucosal Inflammation? A Pilot Study.

INTRODUCTION: The prevalence of patients with food intolerance (FI) has increased significantly. Immunoglobulin (Ig)E-mediated food allergies (FAs) are detected by determining IgE antibodies and skin prick test. Carbohydrate malabsorptions are clarified with breath tests. However, these diagnostic measures cannot capture all intolerances and have limitations in case of gut-mediated FI. The aims of this pilot study were to evaluate different methods to determine intestinal mucosal IgE in patients with FA and to characterize the intestinal mucosa in patients with FI of unknown origin (FH). METHODS: Patients with FA and FH were compared with healthy controls. To determine the IgE antibodies and the cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ of the intestinal mucosal, a lavage was performed as part of an ileocolonoscopy and samples were taken using the cytobrush and biopsy forceps. In a subgroup, mucosal samples were also taken from the duodenum. RESULTS: Data in homogenates of intestinal mucosal samples yielded the highest sensitivity for IgE antibody titers compared with lavage and cytobrush. Patients with FA presented increased intestinal TNF-α and low IFN-γ values. This was in contrast to FH patients, who showed low intestinal IgE antibodies and TNF-α levels, but increased IFN-γ values. DISCUSSION: The determination of IgE antibodies to diagnose intestinal IgE-mediated FA is most reliable in intestinal mucosal samples. Increased TNF-α and low IFN-γ levels in patients with FA characterize an allergic reaction. Decreased TNF-α and increased IFN-γ levels in patients with FH indicate an inflammation-related intolerance reaction (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A520).

Sensibilidad al gluten/trigo no celíaca: Una patología en busca de claros criterios diagnósticos / No disponible

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Immune basis of allergic reactions to food

Food allergies are diseases where the normal tolerance response to oral antigens is altered. Recent advances have begun to uncover mechanisms that mediate sensitization to food allergens and maintenance of the disease. Production of alarmins by epithelial cells triggers a cascade that leads to allergen-specific IgE synthesis. IL-9 has also been shown to play a role in mast cell recruitment and amplification of the allergic response. In recent years, increasing evidence suggests that sensitization to food allergens can be developed via nonoral routes, in particular the skin, thus leading to the "dual exposure hypothesis". Environmental factors such as diet or microbiota can shape the immune system to promote tolerance or sensitization to food antigens. While the mechanism of primary tolerance to food antigens is quite clear, that leading to permanent tolerance in food-allergic individuals through immunotherapy is still under study. Understanding the mechanisms by which oral tolerance is suppressed and sensitization develops will help to identify new targets to develop combined therapies for the treatment of food allergies

La alergia alimentaria es una enfermedad en la que la respuesta fisiológica normal de tolerancia a los antígenos orales se encuentra alterada. Los nuevos avances en la investigación han comenzado a desvelar los mecanismos que median tanto en la sensibilización a los alérgenos alimentarios como en la persistencia de la enfermedad. La producción de alarminas por parte de las células epiteliales desencadena una cascada que conduce a la síntesis de IgE específica frente a los alérgenos alimentarios. También se ha identificado el papel de la IL-9 en el reclutamiento de mastocitos y la amplificación de la respuesta alérgica. Además en estos últimos años se han completado diversas investigaciones que sugieren que la sensibilización a los alérgenos alimentarios puede desarrollarse por vías no orales, en particular a través de la piel, lo cual ha llevado a la propuesta de la denominada "hipótesis de la doble exposición". Por último, factores ambientales como la dieta o la microbiota pueden moldear el sistema inmunológico para promover la tolerancia o la sensibilización a los antígenos alimentarios. Si bien el mecanismo de tolerancia primaria a los antígenos alimentarios es bastante claro, el que conduce a la tolerancia permanente en individuos que ya tienen alergia a los alimentos a través de la inmunoterapia aún está en estudio. Comprender los mecanismos mediante los cuales se suprime la tolerancia oral y se desarrolla la sensibilización ayudará a identificar nuevos objetivos para desarrollar terapias combinadas para el tratamiento de alergias alimentarias

Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study.

BACKGROUND: Most patients with ulcerative colitis (UC) rely predominantly on medication for disease control. Diet interventions can reduce pharmaceutical expenditures and prolong remission. We designed a prospective study to evaluate whether an immunoglobulin G (IgG)-guided exclusion diet would improve symptoms and quality of life (QoL) in patients with UC. METHODS: The 6-month diet intervention included 97 patients with UC, who were randomly divided into an intervention group (n = 49) and a control (n = 48) group. Individual diet plans were created for the intervention group according to IgG titers; the control group ate a healthy diet as normal. Observational indices included disease activity, extraintestinal manifestations, nutritional status, and QoL. Relationships between food-specific IgG antibodies and these indices were also analyzed. RESULTS: At baseline, there were no significant differences between the groups. Food-specific IgG antibodies were detected in 70.10% of participants. After intervention, the Mayo score was significantly lower in the intervention group than in the control group (2.41 ± 0.89 vs 3.52 ± 1.15, P < 0.05). The number of patients with extraintestinal manifestations decreased from 7 to 2 in the intervention group and from 6 to 5 in the control group. As for nutritive indices, the intervention group had higher mean body mass index and albumin than the control group (23.88 ± 3.31 vs 21.50 ± 6.24 kg/m2, respectively, P < 0.05; 48.05 ± 6.39 vs 45.72 ± 5.48 g/L, respectively, P < 0.05), whereas prealbumin and transferrin were not significantly different between the groups. QoL improved after food exclusion (P < 0.05). CONCLUSIONS: An IgG-guided exclusion diet ameliorated UC symptoms and improved QoL. Interactions between IgG-based food intolerance and UC warrant further study.

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.

[The number of intraepithelial lymphocytes in digestive tract in patients with IgG-dependent intolerance of cereal products]. / Liczba limfocytów sródnablonkowych w przewodzie pokarmowym u osób z IgG-zalezna nietolerancja pokarmowa.

Abnormal reaction of food antigens cause a variety disorders of gastrointestinal tract. It is not clear why exactly the same products provoke diarrhea or constipation. AIM: The aim of this study was to assess the number of intraepithelial lymphocytes (IEL) in different parts of gastrointestinal tract in patients with specific IgG antibodies against wheat and secale products. MATERIALS AND METHODS: The study was performed in 36 healthy subjects(group I) and in 70 patients with diarrhea predominant (group II, n=38) or with constipation (group III, n=32). The level of specific IgG antibodies in blood were determined using Food Detective tests (Cambridge Diagnostics). The biopsy material obtained from duodenum, jejunum as well as from right and left colon was used for routine hematoxylin-eosin staining. RESULTS: In group II compared to control group the number of IEL was statistical higher in all part of gastrointestinal tract. Furthermore, in 9 patients (23.6%) in duodenum exceed 30/100 enterocytes, and in colon mucosa exceed 25/100 (21.0%) enterocytes. In patients with constipation (group III) the number of IEL was similar to healthy subjects. CONCLUSIONS: Food intolerance of cereal products may cause immuneinflammatory changes in digestive tract comparable to celiakia and lymphocytic colitis.

Gluten-related disorders: certainties, questions and doubts.

In the last decade, the ingestion of gluten, a heterogeneous complex of proteins present in wheat, rice, barley and probably in oats, has been associated with clinical disorders, such as celiac disease, wheat allergy and recently to non-celiac gluten sensitivity or wheat intolerance syndrome. Gluten-related disorders, which are becoming epidemiologically relevant with an estimated global prevalence of about 5%, require the exclusion of gluten from the diet. For the past 5 years, an important shift in the availability of gluten-free products, together with increased consumption in the general population, has been recorded and is estimated to be about 12-25%. Many people follow a self-prescribed gluten-free diet, despite the fact that the majority have not first been previously excluded, or confirmed, as having gluten disorders. They rely on claims that a gluten-free diet improves general health. In this review, we provide an overview of the clinical disorders related to gluten or wheat ingestion, pointing out the current certainties, open questions, possible answers and several doubts in the management of these conditions. KEY MESSAGE Incidence of gluten-related disorders is increased in the last decade and self-diagnosis is frequent with inappropriate starting of a gluten-free diet. Gluten and wheat are considered as the most important triggers to coeliac disease, wheat allergy and non-celiac gluten sensitivity. Pediatricians, allergologist and gastroenterologist are involved in the management of these conditions and appropriate diagnostic protocols are required.