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Food intolerances are adverse responses to a food component in which the human immune system does not play a direct role, are often dose-dependent, and are not consistently reproducible. Based on the immunological mechanism involved, an FA may be classified as: (a) IgE-mediated, which is one that is mediated by antibodies belonging to immunoglobulin E (IgE); (b) non-IgE, a heterogeneous group of food allergies in which there is an immune reaction against food components, but where the primary pathogenesis is not a product of IgE and thought to act mainly through cell-mediated mechanisms; and (c) mixed, in which both IgE-mediated and cell-mediated immunological mechanisms are involved in the reaction [1,2,4]. An increase in eosinophil and mast cell count was demonstrated in a subgroup of patients with FGIDs along with local and systemic cytokine changes [9,10,11,12,13]. [...]cellular immune activation with increased small bowel homing T cells has been demonstrated to be possible key factors in the clinical manifestations of IBS and FD [14]. Intestinal barrier impairment and microbiota changes (i.e., leaky gut—dysbiosis syndrome) have been documented in patients with FGIDs, and this could allow the penetration of microbial and food allergens into the mucosa, triggering a local inflammatory response that in some cases could spread at the systemic level, predisposing one to a loss of tolerance for self- (autoimmunity) and non-self-innocuous antigens (allergy) [15].

Background Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. Main body A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background ( HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic ‘gold standard’, highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. Conclusions The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.

ObjectiveDifferential diagnosis of villous atrophy (VA) without coeliac antibodies in adults includes seronegative coeliac disease (CD) and chronic enteropathies unrelated to gluten, ie. non-coeliac enteropathies (NCEs). There is currently no international consensus on the nomenclature and diagnostic criteria for these enteropathies. In this work, a Delphi process was conducted to address this diagnostic and clinical uncertainty.DesignAn international task force of 13 gastroenterologists from six countries was recruited at the 16th International Coeliac Disease Symposium, Paris, 2019. Between September 2019 and July 2021, a Delphi process was conducted through mail surveys to reach a consensus on which conditions to consider in the differential diagnosis of VA with negative coeliac serology and the clinical diagnostic approaches required for these conditions. A 70% agreement threshold was adopted.ResultsChronic enteropathies characterised by VA and negative coeliac serology can be attributed to two main clinical scenarios: forms of CD presenting with negative serology, which also include seronegative CD and CD associated with IgA deficiency, and NCEs, with the latter recognising different underlying aetiologies. A consensus was reached on the diagnostic criteria for NCEs assisting clinicians in differentiating NCEs from seronegative CD. Although in adults seronegative CD is the most common aetiology in patients with VA and negative serology, discriminating between seronegative CD and NCEs is key to avoid unnecessary lifelong gluten-free diet, treat disease-specific morbidity and contrast poor long-term outcomes.ConclusionThis paper describes the Paris consensus on the definitions and diagnostic criteria for seronegative CD and chronic NCEs in adults.

To date, the only available treatment for celiac disease (CD) patients is a life-lasting gluten-free diet (GFD). Lack of adherence to the GFD leads to a significant risk of adverse health consequences. Food cross-contamination, nutritional imbalances, and persistent gastrointestinal symptoms are the main concerns related to GFD. Moreover, despite rigid compliance to GFD, patients struggle in achieving a full restoring of the gut microbiota, which plays a role in the nutritive compounds processing, and absorption. Pivotal studies on the supplementation of GFD with probiotics, such as and , reported a potential to restore gut microbiota composition and to pre-digest gluten in the intestinal lumen, reducing the inflammation associated with gluten intake, the intestinal permeability, and the cytokine and antibody production. These findings could explain an improvement in symptoms and quality of life in patients treated with GFD and probiotics. On the other hand, the inclusion of prebiotics in GFD could also be easy to administer and cost-effective as an adjunctive treatment for CD, having the power to stimulate the growth of potentially health-promoting bacteria strains. However, evidence regarding the use of prebiotics and probiotics in patients with CD is still insufficient to justify their use in clinical practice.

Background: The post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to postpartum depression (PPD). Objective: The present clinical study assesses the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4 × 109 CFU/day) on the mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized, Double-Blind, Controlled (RDBPC) trial was carried out on 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4 × 109 CFU/day) plus multivitamins and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 using the Edinburgh Postnatal Depression Scale (EPDS) and the Breastfeeding Self-Efficacy Scale—Short Form (BSES-SF). Results: At days 45 and 90, the probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p < 0.001). Likewise, the breastfeeding quality and the baby’s cries significantly improved in the probiotic group (p < 0.001). Conclusions: Microbiota alterations could influence a post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates that are able to improve stress resilience in the postpartum period.

Amylase/trypsin inhibitors (ATIs) are widely consumed in cereal-based foods and have been implicated in adverse reactions to wheat exposure, such as respiratory and food allergy, and intestinal responses associated with coeliac disease and non-coeliac wheat sensitivity. ATIs occur in multiple isoforms which differ in the amounts present in different types of wheat (including ancient and modern ones). Measuring ATIs and their isoforms is an analytical challenge as is their isolation for use in studies addressing their potential effects on the human body. ATI isoforms differ in their spectrum of bioactive effects in the human gastrointestinal (GI), which may include enzyme inhibition, inflammation and immune responses and of which much is not known. Similarly, although modifications during food processing (exposure to heat, moisture, salt, acid, fermentation) may affect their structure and activity as shown in vitro, it is important to relate these changes to effects that may present in the GI tract. Finally, much of our knowledge of their potential biological effects is based on studies in vitro and in animal models. Validation by human studies using processed foods as commonly consumed is warranted. We conclude that more detailed understanding of these factors may allow the effects of ATIs on human health to be better understood and when possible, to be ameliorated, for example by innovative food processing. We therefore review in short our current knowledge of these proteins, focusing on features which relate to their biological activity and identifying gaps in our knowledge and research priorities.

Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients’ diagnosis, management, and treatment.

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD.

Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) which can affect any part of the whole gastrointestinal tract (from mouth to anus). Malnutrition affects 65–75% of CD patients, and it is now well acknowledged that diet is of paramount importance in the management of the disease. In this review, we would like to highlight the most recent findings in the field of nutrition for the treatment of CD. Our analysis will cover a wide range of topics, from the well-established diets to the new nutritional theories, along with the recent progress in emerging research fields, such as nutrigenomics.