The core gut microbiome, energy balance and obesity

Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.     

Interleukin-5 immunoreactivity and mRNA expression in gut mucosa from patients with food allergy

BACKGROUND: Mast cell activation has been assumed to play a role in dermal neurogenic inflammation: C fibre-derived neuropeptides activating mast cells and releasing histamine, which in turn would activate C fibres. OBJECTIVE: To test this hypothesis mast cell tryptase (MCT) was measured inside the axon reflex flare area. Axon reflexes were elicited by histamine or compound 48/80, a polyanionic mast cell-degranulating substance. The time course of plasma extravasation and release of histamine and MCT from dermal mast cells in neurogenic inflammation was measured in vivo by intradermal microdialysis in humans. METHODS: Single hollow plasmapheresis fibres (pore cutoff size: 3000 kDa) were inserted intracutaneously at the volar forearm and perfused with Ringer's solution (4 microL/min) with one microdialysis fibre located at the planned stimulation site and a second inside the axon reflex area. Neurogenic inflammation was induced by intraprobe delivery of either histamine or the mast cell-degranulating agent compound 48/80. Mediator release was measured at the stimulation sites and inside the arising axon reflex flare area. RESULTS: Mast cell degranulation induced marked plasma protein extravasation (PPE 0.25 +/- 0.04-1.31 +/- 0.6 mg/mL; pre- and post-stimulation, mean +/- sem, n = 7) and release of histamine (2.0 +/- 0.9-38.7 +/- 1.4 ng/mL) and MCT (9.84 +/- 2.4-92.2 +/- 21.6 ng/mL). Interestingly, in addition to increasing PPE (0.33 +/- 0. 11-1.85 +/- 0.9 mg/mL), histamine also induced a slight but significant increase in MCT (11.3 +/- 3.0-12.4 +/- 2.3 ng/mL). No evidence for mast cell activation was observed inside the axon reflex areas, where PPE (0.34 +/- 0.03-0.25 +/- 0.02 mg/mL), histamine (1.64 +/- 0.5-1.46 +/- 0.4 ng/mL) and MCT concentration (11.6 +/- 3.1-7.6 +/- 1.7 ng/mL) gradually decreased. CONCLUSION: It is concluded that dermal neurogenic inflammation does not degranulate mast cells.     

The epidemiology of food allergy

In contrast to respiratory allergies, the epidemiology of food allergy has been little studied, and there is no strong evidence for an increasing incidence, either among infants and children or in adults. Neither are there any studies showing regional differences in prevalence. On the contrary, studies in Estonia, Iceland and Sweden indicate a similar prevalence during the first 2 years of life, both in verified food allergy and reported food intolerance. This is despite a low prevalence of respiratory allergies in the two former countries and a high prevalence in Sweden. The major problem with such epidemiological studies lies in the fact that there are no simple diagnostic criteria to verify the diagnosis. So far IgE determinations have been the only available diagnostic test, and their value is limited by poor sensitivity and the fact that at best they would only verify a small proportion of food intolerance, i.e. that caused by IgE-mediated reactions. A diagnosis of food allergy/intolerance must be based on a double-blind placebo-controlled food challenge, and not on the patient's or doctor's impression. More studies are required from different regions in order to identify similarities and differences in the patterns of food allergy. In particular, there is a need for properly conducted epidemiological studies in adults. Such studies should be interdisciplinary, as the cultural and social perceptions of food allergy and food intolerance would be expected to have a major impact on prevalence, perhaps even more than medical factors.     

The epidemiology of food allergy in adults

The prevalence and awareness of food allergy (FA) among US adults is arguably at a historical high, both with respect to primary immunoglobulin E–mediated food hypersensitivity and other food-triggered conditions that operate through a variety of immunologic mechanisms (eg, pollen-FA syndrome, alpha-gal syndrome, food protein-induced enterocolitis syndrome, eosinophilic esophagitis). Worryingly, not only are many adults retaining childhood-onset food allergies as they age into adulthood, it seems that many adults are experiencing adult-onset allergies to previously tolerated foods, with correspondingly adverse physical, and psychological health impacts. Consequently, this review aims to summarize what is currently known about the epidemiology and population-level burden of FA among adult populations in North America and around the globe. This article also provides insights into the natural history of these conditions and what we need to know as we look to the future to support effective care and prevent FA.     

Antigen-specific secretory IgA antibodies in the gut are decreased in a mouse model of food allergy

BACKGROUND: A large body of evidence implicates IgA antibodies in the immune response to pathogens present in the gut. Whether IgA antibodies play a similar role in food allergy remains to be determined. OBJECTIVE: We sought to characterize beta-lactoglobulin (BLG)-specific serum and secretory IgA antibody production in the gut and to define the role of antigen-induced cytokines in IgA production in a murine model of food allergy. METHODS: BLG-specific IgA antibodies were measured in the sera and feces of mice anaphylactic or tolerant to BLG. The number of antibody-secreting cells in the spleen and Peyer's patches was determined by means of ELISPOT. Mesenteric lymph node cells and Peyer's patch T cells were transferred to naive mice, and antibody production in the sera and feces in recipient mice, as well as antibody-secreting cell numbers, were measured. RESULTS: Serum IgA antibody titers were strongly increased in anaphylactic mice. In contrast, BLG-specific IgA antibody titers were increased in feces but not in sera from tolerant mice. These results were correlated with an increased number of BLG-specific IgA-secreting cells in Peyer's patches from tolerant mice. The adoptive transfer of Peyer's patch CD3+ cells from tolerant mice induced an increased number of IgA-secreting cells preferentially in the Peyer's patches of naive recipient mice. Furthermore, an increase of BLG-induced IL-10 and TGF-beta levels was found at IgA production sites. CONCLUSIONS: These results suggest a role for secretory IgA in tolerance mechanisms to foods. Peyer's patch CD3+ cells are primarily involved by favoring IgA production through the release of IL-10 and TGF-beta.     

The future of food allergy therapeutics

Food allergy is increasing in prevalence in westernized countries, leading to significant morbidity including nutritional deficiencies and growth delay as well as psychosocial burdens and the potential for fatal anaphylaxis. There is currently no effective form of therapy, and the mainstay of treatment remains strict avoidance. However, there are a number of promising therapeutic strategies currently being investigated for the treatment of food allergies. Allergen-specific approaches, such as various forms of immunotherapy, have been a major focus of investigation and appear to be promising methods of desensitization. More recently, the addition of anti-IgE monoclonal antibodies (mAbs) to immunotherapy regimens has been studied. Early work with antigen-fixed leukocytes in a murine model has shown promise in inducing tolerance, as have vaccines containing modified recombinant food proteins coadministered with heat-killed Escherichia coli. Nonspecific approaches include a Chinese herbal formulation, anti-IgE mAbs, and Trichuris suis ova therapy. The array of treatment modalities currently being investigated increases the likelihood of finding one or more effective therapies for the treatment of food allergy.     

The threshold concept in food safety and its applicabilityto food allergy

Down the years there have been many clinical reports of exquisite sensitivity to low doses of food allergens. There are many factors that may contribute to a variation of threshold in an individual exposed to an allergen during the course of his or her daily life. Some of these factors are intrinsic and unavoidable. Other factors may be predictable but not easily controllable, such as asthma, exposure to allergens during the pollen season and predicting situations that may be risky. Other factors may be out of the control of the individual. The most important one of these is the adequate training and awareness of manufacturers and caterers who aim to provide safe and nutritious meals to their allergic and non-allergic customers alike. Clinical histories of reactions in the community and the use of labial exposure during food challenge show that most non-ingestion exposures to peanut usually result in easily treated minor reactions. Formal, oral food challenges have shown that low dose reactivity is relatively common but studies have not yet had the power to investigate whether peanut allergy is more commonly associated with very low dose reactivity than other foods. This means that industry must not concentrate only on peanut and tree nuts when looking at issues of contamination just because they are associated with the majority of severe reactions. There are more milk and egg allergic children in the general population and they deserve the same protection from allergen exposure as sufferers of peanut or tree nut allergies.     

The role of dendritic cells in food allergy

In recent years, our understanding of the initiation of T(H)2-type immunity has increased significantly, yet the mechanism behind the induction of T(H)2 responses and allergic sensitization to food antigens largely remains an enigma. Dendritic cells (DCs) were first described almost 4 decades ago and have since been recognized as the most important antigen-presenting cells and crucial in the induction of T-cell differentiation. Here we discuss our current knowledge of the role of DCs in food allergy. In both murine models and allergic patients, characteristics of DCs have been identified that might play a role in sensitization to food and enhance susceptibility to food allergy. In addition, it has now been shown that several allergens, including some from foods, can directly activate DCs to induce T(H)2 skewing. Other cell types with innate immune functions, such as epithelial cells and basophils, might also be involved in sensing of food allergens in human subjects, and interaction of DCs with these cells might facilitate sensitization. DCs appear to play an important role in allergen-specific immunotherapy and could be an attractive target for tolerance induction in patients with food allergy. Further characterization of differences in DC responses between human food-allergic and nonallergic subjects is necessary to gain a better insight into the role of DCs in sensitization and tolerance to food allergens.