A comprehensive review on natural bioactive compounds and probiotics as potential therapeutics in food allergy treatment

Food allergy is rising at an alarming rate and is a major public health concern. Globally, food allergy affects over 500 million people, often starting in early childhood and increasingly reported in adults. Commercially, only one approved oral immunotherapy-based treatment is currently available and other allergen-based immunotherapeutic are being investigated in clinical studies. As an alternative approach, a substantial amount of research has been conducted on natural compounds and probiotics, focusing on the immune modes of action, and therapeutic uses of such sources to tackle various immune-related diseases. Food allergy is primarily mediated by IgE antibodies and the suppression of allergic symptoms seems to be mostly modulated through a reduction of allergen-specific IgE antibodies, upregulation of blocking IgG, and downregulation of effector cell activation (e.g., mast cells) or expression of T-helper 2 (Th-2) cytokines. A wide variety of investigations conducted in small animal models or cell-based systems have reported on the efficacy of natural bioactive compounds and probiotics as potential anti-allergic therapeutics. However, very few lead compounds, unlike anti-cancer and anti-microbial applications, have been selected for clinical trials in the treatment of food allergies. Natural products or probiotic-based approaches appear to reduce the symptoms and/or target specific pathways independent of the implicated food allergen. This broad range therapeutic approach essentially provides a major advantage as several different types of food allergens can be targeted with one approach and potentially associated with a lower cost of development. This review provides a brief overview of the immune mechanisms underlying food allergy and allergen-specific immunotherapy, followed by a comprehensive collection of current studies conducted to investigate the therapeutic applications of natural compounds and probiotics, including discussions of their mode of action and immunological aspects of their disease-modifying capabilities

Recombinant Tropomyosin from the Pacific Oyster (Crassostrea gigas) for Better Diagnosis

The Pacific oyster is a commercially important mollusc and, in contrast to most other shellfish species, frequently consumed without prior heat treatment. Oysters are rich in many nutrients but can also cause food allergy. Knowledge of their allergens and cross-reactivity remains very limited. These limitations make an optimal diagnosis of oyster allergy difficult, in particular to the Pacific oyster (Crassostrea gigas), the most cultivated and consumed oyster species worldwide. This study aimed to characterise IgE sensitisation profiles of 21 oyster-sensitised patients to raw and heated Pacific oyster extract using immunoblotting and advanced mass spectrometry, and to assess the relevance of recombinant oyster allergen for improved diagnosis. Tropomyosin was identified as the major allergen recognised by IgE from 18 of 21 oyster-sensitised patients and has been registered with the WHO/IUIS as the first oyster allergen (Cra g 1). The IgE-binding capacity of oyster-sensitised patients’ IgE to purified natural and recombinant tropomyosin from oyster, prawn, and dust mite was compared using enzyme-linked immunosorbent assay. The degree of IgE binding varied between patients, indicating partial cross-sensitisation and/or co-sensitisation. Amino acid sequence alignment of tropomyosin from these three species revealed five regions that contain predicted IgE-binding epitopes, which are most likely responsible for this cross-reactivity. This study fully biochemically characterises the first and major oyster allergen Cra g 1 and demonstrates that the corresponding recombinant tropomyosin should be implemented in improved component-resolved diagnostics and guide future immunotherapy

Thermostable allergens in canned fish: Evaluating risks for fish allergy

Background: Major fish allergens, including parvalbumin (PV), are heat stable and can withstand extensive cooking processes. Thus, the management of fish allergy generally relies on complete avoidance. Fish-allergic patients may be advised to consume canned fish, as some fish-allergic individuals have reported tolerance to canned fish. However, the safety of consuming canned fish has not been evaluated with comprehensive immunological and molecular analysis of canned fish products. Methods: We characterized the in vitro immunoreactivity of serum obtained from fish-allergic subjects to canned fish. Seventeen canned fish products (salmon n = 8; tuna n = 7; sardine n = 2) were assessed for the content and integrity of PV using allergen-specific antibodies. Subsequently, the sIgE binding of five selected products was evaluated for individual fish-allergic patients (n = 53). Finally, sIgE-binding proteins were identified by mass spectrometry. Results: The canned fish showed a markedly reduced PV content and binding to PV-specific antibodies compared with conventionally cooked fish. However, PV and other heat-stable fish allergens, including tropomyosin and collagen, still maintained their sIgE-binding capacity. Of 53 patients, 66% showed sIgE binding to canned fish proteins. The canned sardine contained proteins bound to sIgE from 51% of patients, followed by canned salmon (43%–45%) and tuna (8%–17%). PV was the major allergen in canned salmon and sardine. Tropomyosin and/or collagen also showed sIgE binding. Conclusion: We showed that canned fish products may not be safe for all fish-allergic patients. Canned fish products should only be considered into the diet of individuals with fish allergy, after detailed evaluation which may include in vitro diagnostics to various heat-stable fish allergens and food challenge conducted in suitable environments

Novel allergen discovery through comprehensive de novo transcriptomic analyses of five shrimp species

Shellfish allergy affects 2% of the world's population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among shellfish species and between allergenic invertebrates such as dust mites, the underlying molecular basis is not well understood. Here we mine the complete transcriptome of five frequently consumed shrimp species to identify and compare allergens with all known allergen sources. The transcriptomes were assembled de novo, using Trinity, from raw RNA-Seq data of the whiteleg shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), banana shrimp (Fenneropenaeus merguiensis), king shrimp (Melicertus latisulcatus), and endeavour shrimp (Metapenaeus endeavouri). BLAST searching using the two major allergen databases, WHO/IUIS Allergen Nomenclature and AllergenOnline, successfully identified all seven known crustacean allergens. The analyses revealed up to 39 unreported allergens in the different shrimp species, including heat shock protein (HSP), alpha-tubulin, chymotrypsin, cyclophilin, beta-enolase, aldolase A, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Multiple sequence alignment (Clustal Omega) demonstrated high homology with allergens from other invertebrates including mites and cockroaches. This first transcriptomic analyses of allergens in a major food source provides a valuable resource for investigating shellfish allergens, comparing invertebrate allergens and future development of improved diagnostics for food allergy

The Algal Polysaccharide Ulvan and Carotenoid Astaxanthin Both Positively Modulate Gut Microbiota in Mice

The intestinal microbial community (microbiota) is dynamic and variable amongst individuals and plays an essential part in gut health and homeostasis. Dietary components can modulate the structure of the gut microbiota. In recent years, substantial efforts have been made to find novel dietary components with positive effects on the gut microbial community structure. Natural algal polysaccharides and carotenoids have been reported to possess various functions of biological relevance and their impact on the gut microbiota is currently a topic of interest. This study, therefore, reports the effect of the sulfated polysaccharide ulvan and the carotenoid astaxanthin extracted and purified from the aquacultured marine green macroalgae Ulva ohnoi and freshwater green microalgae Haematococcus pluvialis, respectively, on the temporal development of the murine gut microbiota. Significant changes with the increase in the bacterial classes Bacteroidia, Bacilli, Clostridia, and Verrucomicrobia were observed after feeding the mice with ulvan and astaxanthin. Duration of the treatments had a more substantial effect on the bacterial community structure than the type of treatment. Our findings highlight the potential of ulvan and astaxanthin to mediate aspects of host-microbe symbiosis in the gut, and if incorporated into the diet, these could assist positively in improving disease conditions associated with gut health

Commercial shellfish skin prick test extracts show critical variability in allergen repertoire

[Extract] Crustacean and mollusc (shellfish) allergy affects up to 3% of the general population, is usually lifelong and commonly triggers anaphylaxis.1 Allergen repertoire diversity among hundreds of edible shellfish species worldwide is poorly reflected in available in vivo and in vitro diagnostic tools for shellfish allergy. Skin prick testing (SPT) is often the preferred first-line diagnostic approach. However, widely utilized commercial SPT extracts are generally not standardized, limiting the diagnostic value of results.2 Asero et al. reported a heterogeneous abundance of three shellfish allergens in five commercial crustacean SPT extracts, resulting in 32 clinical profiles among 157 shrimp-allergic patients.3 In 2019, we demonstrated considerable variability in allergen repertoire and IgE-binding for 27 commercial fish SPT extracts.4 We now report an even greater, critical variability for 11 commercial crustacean and five mollusc SPT extracts, utilizing biochemical and immunological methods and mass spectrometry (see Appendix S1 for methodology and TableS1 for allergen extract details)

The first reptilian allergen and major allergen for fish-allergic patients: Crocodile β-parvalbumin

Background: Clinical cross-reactivity between bony fish, cartilaginous fish, frog, and chicken muscle has previously been demonstrated in fish-allergic patients. In indicative studies, two reports of anaphylaxis following the consumption of crocodile meat and IgE-cross-binding were linked to the major fish allergen parvalbumin (PV). This study investigates IgE-binding proteins in crocodile meat with a focus on PV and their clinical relevance. Methods: Proteins were extracted from muscle tissue of crocodile, three bony fish, and two cartilaginous fish. A cohort of fish-allergic pediatric patients (n = 77) underwent allergen skin prick testing (SPT) to three fish preparations (n = 77) and crocodile (n = 12). IgE-binding proteins were identified and quantified by SDS-PAGE, mass spectrometric analyses, and immunoblotting using commercial and in-house antibodies, as well as individual and pooled patients’ serum. PV isoforms were purified or recombinantly expressed before immunological analyses, including human mast cell degranulation assay. Results: Of the tissues analyzed, PV was most abundant in heated crocodile preparation, triggering an SPT of ≥3 mm in 8 of 12 (67%) fish-allergic patients. Seventy percent (31 of 44) of fish PV-sensitized patients demonstrated IgE-binding to crocodile PV. Crocodile β-PV was the major IgE-binding protein but 20-fold less abundant than α-PV. Cellular reactivity was demonstrated for β-PV and epitopes predicted, explaining frequent IgE-cross-binding of β-PVs. Both PV isoforms are now registered as the first reptile allergens with the WHO/IUIS (β-PV as Cro p 1 and α-PV as Cro p 2). Conclusion: Fish-allergic individuals may be at risk of an allergy to crocodile and should seek specialist advice before consuming crocodilian meat

Collagen-an important fish allergen for improved diagnosis

Background Fish collagen is widely used in medicine, cosmetics, and the food industry. However, its clinical relevance as an allergen is not fully appreciated. This is likely due to collagen insolubility in neutral aqueous solutions, leading to low abundance in commercially available in vitro and skin prick tests for fish allergy. Objective To investigate the relevance of fish collagen as an allergen in a large patient population (n = 101). Methods Acid-soluble collagen type I was extracted from muscle and skin of Atlantic salmon, barramundi, and yellowfin tuna. IgE binding to collagen was analyzed by ELISA for 101 fish-allergic patients. Collagen-sensitized patients' sera were tested for IgE binding to parvalbumin from the same fish species. IgE cross-linking was analyzed by rat basophil leukemia assay and basophil activation test. Protein identities were confirmed by mass spectrometry. Results Purified fish collagen contained type I α1 and α2 chains and their multimers. Twenty-one of 101 patients (21%) were sensitized to collagen. Eight collagen-sensitized patients demonstrated absence of parvalbumin-specific IgE to some fish species. Collagen induced functional IgE cross-linking, as shown by rat basophil leukemia assay performed using 6 patients' sera, and basophil activation test using fresh blood from 1 patient. Collagen type I α chains from barramundi and Atlantic salmon were registered at www.allergen.org as Lat c 6 and Sal s 6, respectively. Conclusions IgE sensitization and IgE cross-linking capacity of fish collagen were demonstrated in fish-allergic patients. Inclusion of relevant collagen allergens in routine diagnosis is indicated to improve the capacity to accurately diagnose fish allergy

Optimal foreign borrowing: The impact of the planning horizon on the half and full debt cycle

Shrimp is one of the predominant causes of food allergy among adults, often presenting with severe reactions. Current in vitro diagnostics are based on quantification of patient specific-IgE (sIgE) to shrimp extract. Tropomyosin is the known major shrimp allergen, but IgE sensitisation to other allergens is poorly characterised. In this study, the binding of IgE to various shrimp allergens, additional to tropomyosin, was investigated using sera from 21 subjects who had clinical reactions to one or more shellfish species. Total shrimp-sIgE was quantified using ImmunoCAP, while allergen-sIgEs were quantified using immunoblotting and mass spectrometry, and immuno-PCR to recombinant shrimp tropomyosin. Sixty-two percent of subjects (13/21) were positive to shrimp by ImmunoCAP. IgE from 43% of subjects (9/21) bound tropomyosin, while an additional 29% of subjects (6/21) demonstrated IgE-binding solely to other shrimp allergens, including sarcoplasmic calcium-binding protein, arginine kinase and hemocyanin. Furthermore, IgE sensitisation to other shrimp allergens was demonstrated in 50% of subjects (4/8) who were ImmunoCAP negative. The lack of standardised shrimp allergens and inadequacy of current extracts for shrimp allergy diagnosis is highlighted by this study. Comprehensive knowledge of less studied allergens and their inclusion in component-resolved diagnostics will improve diagnostic accuracy, benefitting the wider population suffering from shellfish allergy

The malaria war

The 25th of April is a national day to honour the members of the Australian and New Zealand Army Corps (ANZAC), who gave their lives at Gallipoli during the First World War (WWI). The 25th of April has also been designated World Malaria Day by the World Health Organization (WHO), and is commemorated every year to bring awareness of deaths caused by malaria infection and global efforts to control infection. There is no coincidence that these two commemorative events are on the same day, as military campaigns suffered great burdens caused by malaria infection during WWI. Malaria infection is yet to be eradicated from human history; fundamental discoveries of malaria and its control were developed during WWI and the fight against malaria continues to this date. This article focuses on the discovery of malaria prior to WWI, the impact that malaria had on military in the war, and the development of control measures taken to minimize these effects and to subsequently eradicate the disease in many countries