Food Intolerance and Food Allergy: Novel Aspects in a Changing World

Background: Seafood allergy is a significant global health concern that greatly impacts a patient’s quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case–control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case–control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = −1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = −0.63, p < 0.01, I² = 0), arginine kinase allergen (MD = −0.83, p < 0.01, I² = 0), and Maillard reaction processing method (MD = −0.65, p < 0.01, I² = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary. Full article

Histamine intolerance (HIT) is a clinical condition caused by decreased intestinal degradation of ingested histamine, primarily due to reduced enzyme diamine oxidase (DAO) activity, leading to histamine accumulation and causing various clinical manifestations. The measurement of serum DAO is commonly used as the main diagnostic test for HIT, although its diagnostic use is still uncertain. In this retrospective study, we aimed to assess the validity of DAO determination in patients with clinically suspected HIT. We measured DAO levels in 249 patients with suspected HIT and 50 healthy adult controls without HIT-related problems. Based on five clinical criteria, we divided patients into two groups: high (all five inclusion criteria; 41 patients) and low probability of HIT (≤4 inclusion criteria; 208 patients). Patients with a “high probability of HIT” had the lowest DAO (median: 8 U/mL, IQR: 6–10) in comparison to patients with a “low probability of HIT (median: 10 U/mL, IQR: 7–16, p = 0.0006) and healthy controls (median: 18 U/mL, IQR: 14–22, p < 0.0001). The specificity and sensitivity for DAO levels < 3/< 10 U/mL (manufacturer’s set cut-off) to discriminate between patients with ‘‘high probability of HIT’’ and healthy controls were 100%/92% and 2%/71%. On the other hand, the specificity and sensitivity to discriminate between patients with ‘‘high probability of HIT’’ and ‘‘low probability of HIT’’ were 97%/61% and 2%/71%, respectively. Serum DAO determination represents an additional asset to the diagnosis of HIT based on clinical evaluation and assessment, but the diagnosis should not solely rely on DAO measurements. Full article

Introduction: The role of a gluten-free diet (GFD) in Non-Coeliac Gluten/Wheat Sensitivity (NCGWS) is unclear. We present the largest study comparing adherence to a GFD in patients with Coeliac Disease (CD) and NCGWS and assess its impact on quality of life (QoL) and sleep in patients with NCGWS. Methods: Patients with NCGWS at a tertiary centre completed the Coeliac Disease Adherence Test (CDAT), Coeliac Symptom Index (CSI) and Sleep Condition Indicator (SCI). Higher CDAT scores indicate worse adherence, higher CSI scores indicate poorer QoL, and higher SCI scores indicate better sleep. CDAT scores were correlated with CSI and SCI scores. A second group of patients with CD completed the CDAT questionnaire only. Results were compared with the CDAT responses from the NCGWS group. Results: For the NCGWS cohort (n = 125), the median CDAT score was 17/35, indicating poor adherence. The median CSI score was 44/80, with 40% of scores associated with a poor QoL. The median SCI score was 14/32, and DSM-V criteria for insomnia was met by 42% of patients. There was a positive correlation between CSI and CDAT scores (r = 0.59, p < 0.0001) and a negative correlation between SCI and CDAT scores (r = −0.37, p = 0.0002). In the CD cohort (n = 170), the median CDAT score was 13/35. Patients with NCGWS had poorer adherence compared to CD (CDAT: 17.0 vs. 13.0, respectively, p = 0.0001). Conclusion: Patients with NCGWS adhere to a GFD less than those with CD. Poorer adherence to a GFD in patients with NCGWS correlates with a worse QoL and sleep performance. Full article

Background: Non-celiac wheat sensitivity (NCWS) is a poorly understood gluten-related disorder (GRD) and its prominent symptoms can be ameliorated by gluten avoidance. This study aimed to determine the effectiveness of a probiotic mixture in hydrolyzing gliadin peptides (toxic components of gluten) and suppressing gliadin-induced inflammatory responses in Caco-2 cells. Methods: Wheat dough was fermented with a probiotic mix for 0, 2, 4, and 6 h. The effect of the probiotic mix on gliadin degradation was monitored by SDS-PAGE. The expression levels of IL-6, IL-17A, INF-γ, IL-10, and TGF-β were evaluated using ELISA and qRT-PCR methods. Results: According to our findings, fermenting wheat dough with a mix of B. longum, L. acidophilus, and L. plantarum for 6 h was effective in gliadin degradation. This process also reduced levels of IL-6 (p = 0.004), IL-17A (p = 0.004), and IFN-γ (p = 0.01) mRNA, as well as decreased IL-6 (p = 0.006) and IFN-γ (p = 0.0009) protein secretion. 4 h fermentation led to a significant decrease in IL-17A (p = 0.001) and IFN-γ (p = 0.003) mRNA, as well as reduced levels of IL-6 (p = 0.002) and IFN-γ (p < 0.0001) protein secretion. This process was also observed to increase the expression levels of IL-10 (p < 0.0001) and TGF-β (p < 0.0001) mRNA. Conclusions: 4 h fermentation of wheat flour with the proposed probiotic mix might be a good strategy to develop an affordable gluten-free wheat dough for NCWS and probably other GRD patients. Full article

During the last decades, plant-based milk has become very appreciated by consumers, becoming a staple ingredient, especially for alternative breakfasts. Milk contains lactose, which is a sugar hydrolysed by the lactase enzyme. Lactose intolerance and lactose malabsorption are very common food intolerances among individuals. However, a lot of consumers consider themselves as lactose intolerant on the basis of self-reported intolerance and start to avoid dairy products, ignoring that plant-based milk alternatives are not nutritionally comparable to animal milk, especially in terms of protein intake. The aim of this study is to grow folder knowledge of the security of plant-based drinks, helping competent authorities to issue a risk assessment and to apply national plans about consumer safety. Results show that proper sanitary practices, such as pasteurization, are necessary in plant-based milk alternatives as well as in dairy milk. Chemical analysis has highlighted that there are no pesticide risks for consumers. Full article

The hypothesis is that inflammatory/allergic conditions should be considered in self-reported milk intolerance (SRMI) patients who test negative and/or are asymptomatic at Lactose Hydrogen Breath Test (LHBT). We analyzed fecal calprotectin (FCP) values in SRMI patients to investigate the frequency of a “positive” intestinal inflammation marker and its correlation with lactose tolerance/intolerance. Data from 329 SRMI patients were retrospectively analyzed; according to the positive/negative results (maldigester/digester) and the presence/absence of symptoms reported during LHBT (intolerant/tolerant), patients were divided into: ‘lactose tolerants’ (n. 104), ‘maldigesters/intolerants’ (n. 187), ‘digesters/intolerants’ (n. 38). FCP values were analyzed in all three subgroups. A percentage of SRMI patients complained of constipation (>15%), extraintestinal symptoms (>30% including anemia), multiple food hypersensitivity (7.6%) and had intraepithelial lymphocytic infiltration at duodenal biopsy (>50%). Over 50.0% showed FCP values above the normal limit. Lactose tolerants and maldigesters/intolerants had higher positivity frequencies (p < 0.0001, for both) and absolute values (p = 0.04, for maldigesters/intolerants) of FCP compared to digesters/intolerants. FCP was not useful to differentiate tolerant from intolerant subjects (AUC 0.58). Our data suggest the existence of an allergic/inflammatory pathogenetic mechanism in a subset of SRMI subjects. FCP results are in keeping with this hypothesis, even if they cannot differentiate lactose tolerant from intolerant patients. Full article

Food allergy represents a global health problem impacting patients’ and caregivers’ quality of life and contributing to increased healthcare costs. Efforts to identify preventive measures starting from pregnancy have recently intensified. This review aims to provide an overview of the role of maternal factors in food allergy prevention. Several studies indicate that avoiding food allergens during pregnancy does not reduce the risk of developing food allergies. International guidelines unanimously discourage avoidance diets due to potential adverse effects on essential nutrient intake and overall health for both women and children. Research on probiotics and prebiotics during pregnancy as preventive measures is promising, though evidence remains limited. Consequently, guidelines lack specific recommendations for their use in preventing food allergies. Similarly, given the absence of conclusive evidence, it is not possible to formulate definitive conclusions on the supplementation of vitamins, omega-3 fatty acids (n-3 PUFAs), and other antioxidant substances. A combination of maternal interventions, breastfeeding, and early introduction of foods to infants can reduce the risk of food allergies in the child. Further studies are needed to clarify the interaction between genetics, immunological pathways, and environmental factors Full article

A lifelong gluten-free diet (GFD) is the only treatment for celiac disease and other gluten-related disorders. Nevertheless, strict adherence to the GFD is often challenging due to concerns about social isolation, risk of gluten contaminations, high cost, poor quality and the taste of gluten-free products. Moreover, although the GFD is effective in achieving mucosal healing, it may lead to dietary imbalances due to nutrient deficiencies over a long period of time. To overcome these issues, several gluten-free wheat flours have been developed to create products that closely resemble their gluten-containing counterparts. Furthermore, given the critical importance of adhering to the GFD, it becomes essential to promote adherence and monitor possible voluntary or involuntary transgressions. Various methods, including clinical assessment, questionnaires, serology for celiac disease, duodenal biopsies and the detection of Gluten Immunogenic Peptides (GIPs) are employed for this purpose, but none are considered entirely satisfactory. Since adherence to the GFD poses challenges, alternative therapies should be implemented in the coming years to improve treatment efficacy and the quality of life of patients with celiac disease. The aim of this narrative review is to explore current knowledge of the GFD and investigate its future perspectives, focusing on technology advancements, follow-up strategies and insights into a rapidly changing future. Full article

Cow’s milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, “lactase-deficient” individuals cannot digest milk’s main carbohydrate, lactose, depriving themselves of highly beneficial milk proteins like casein, lactoalbumin, and lactoglobulin due to lactose intolerance (LI), while other individuals develop allergies specifically against these proteins (CMPA). The management of these conditions differs, and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restrictions or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of nutrients on the genome, proteome, and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and increasing life expectancy. Here, we report the opinion of the scientific community proposing to replace the “one size fits all” approach with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety often resulting from the individual perception of this condition as different from a normal state. Full article

Background: Allergic disease, including food allergies (FA)s, has been identified as a major global disease. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility”, during which several factors can predispose children to FA development. Changes in the composition of the gut microbiota from pregnancy to infancy may play a pivotal role in this regard: some bacterial genera, such as Lactobacillus and Bifidobacterium, seem to be protective against FA development. On the contrary, Clostridium and Staphylococcus appear to be unprotective. Methods: We conducted research on the most recent literature (2013–2023) using the PubMed and Scopus databases. We included original papers, clinical trials, meta-analyses, and reviews in English. Case reports, series, and letters were excluded. Results: During pregnancy, the maternal diet can play a fundamental role in influencing the gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species via human milk oligosaccharides (HMOs), which play a prebiotic role. Moreover, complementary feeding can modify the gut microbiota’s composition. Conclusions: The first two years of life are a critical period, during which several factors can increase the risk of FA development in genetically predisposed children. Full article

Allergies are a common and increasing health problem affecting millions of people worldwide. This increase is attributed to genetic predisposition, air pollution, climate change, lack of physical activity, and alterations in eating habits. The Mediterranean diet (MD), which includes a lot of fruits and vegetables, whole grains, legumes, nuts, olive oil, and fish, has been linked to a variety of health benefits, including a lower risk of chronic and allergic disease. This paper explores the effects of the dietary components of the MD on food allergies. Electronic databases PubMed, Scopus, Science Direct, and EBSCO were used to conduct this systematic review. Out of 696 studies initially identified, five human and four animal studies were included. Risk of bias was determined using the Office of Health Assessment and Translation tool. In human studies, when the intervention was given during pregnancy and lactation, a beneficial effect was observed. When the intervention was given during pregnancy and until birth or to the infant for six months, no effect was observed. The animal studies indicated a beneficial effect between the food components of the MD and food allergies. Although the results are promising, the limited number of studies highlights the need for more research. Full article

We report on a group of patients with gluten sensitivity with and without coeliac disease presenting with unexplained sensory symptoms in the absence of structural pathology. Methods: The patients were selected from the gluten neurology clinic based at the Royal Hallamshire Hospital, Sheffield, UK, on the basis of sensory symptoms but normal neuroaxis imaging and peripheral nerve evaluation. Results: A total of 30 patients were identified with a mean age at presentation of 47 years. The prevalence of enteropathy was 78%. The sensory disturbance was characterised by tingling at 50%, numbness at 27%, pain at 20%, burning at 13% and “buzzing” feeling at 7%. The distribution of the sensory symptoms included hands and feet in 27% of the patients, torso in 27%, legs only in 23%, face in 17% and arms only in 10%. For five patients, the sensory disturbance was migratory and affected different parts of the body at any given time. After the introduction of a gluten-free diet, 77% of patients noted significant improvement in their sensory symptoms. In one-third of the patients, there was a complete resolution of the sensory symptoms. Conclusion: Unexplained sensory symptoms can be seen in patients with gluten sensitivity and respond to strict adherence to a gluten-free diet. Full article