Purpose of Review The incidence of allergies is increasing and has been associated with several environmental factors including westernized diets. Changes in environment and nutrition can result in dysbiosis of the skin, gut, and lung microbiota altering the production of microbial metabolites, which may in turn generate epigenetic modifications. The present review addresses studies on pectin-mediated effects on allergies, including the immune modulating mechanisms by bacterial metabolites. Recent Findings Recently, microbiota have gained attention as target for allergy intervention, especially with prebiotics, that are able to stimulate the growth and activity of certain microorganisms. Dietary fibers, which cannot be digested in the gastrointestinal tract, can alter the gut microbiota and lead to increased local and systemic concentrations of gut microbiota-derived short chain fatty acids (SCFAs). These can promote the generation of peripheral regulatory T cells (Treg) by epigenetic modulation and suppress the inflammatory function of dendritic cells (DCs) by transcriptional modulation. The dietary fiber pectin (a plant-derived polysaccharide commonly used as gelling agent and dietary supplement) can alter the ratio of Firmicutes to Bacteroidetes in gut and lung microbiota, increasing the concentrations of SCFAs in feces and sera, and reducing the development of airway inflammation by suppressing DC function. Summary Pectin has shown immunomodulatory effects on allergies, although the underlying mechanisms still need to be elucidated. It has been suggested that the different types of pectin may exert direct and/or indirect immunomodulatory effects through different mechanisms. However, little is known about the relation of certain pectin structures to allergies.

Pathogen‐induced inflammation comprises pro‐ and anti‐inflammatory processes, which ensure pathogen removal and containment of the proinflammatory activities. Here, we aimed to identify the development of inflammatory microenvironments and their maintenance throughout the course of a toll‐like receptor 2‐mediated paw inflammation. Within 24 h after pathogen‐injection, the immune cells were organized in three zones, which comprised a pathogen‐containing “core‐region”, a bordering proinflammatory (PI)‐region and an outer anti‐inflammatory (AI)‐region. Eosinophils were present in all three inflammatory regions and adapted their cytokine profile according to their localization. Eosinophil depletion reduced IL‐4 levels and increased edema formation as well as mechanical and thermal hypersensitivities during resolution of inflammation. Also, in the absence of eosinophils PI‐ and AI‐regions could not be determined anymore, neutrophil numbers increased, and efferocytosis as well as M2‐macrophage polarization were reduced. IL‐4 administration restored in eosinophil‐depleted mice PI‐ and AI‐regions, normalized neutrophil numbers, efferocytosis, M2‐macrophage polarization as well as resolution of zymosan‐induced hypersensitivity. In conclusion, IL‐4‐expressing eosinophils support the resolution of inflammation by enabling the development of an anti‐inflammatory framework, which encloses proinflammatory regions.

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Seit der ersten Mitteilung von H e i n s e n und H a g e n (149) über das Auftreten einer eigentümlichen Abnahme der Tablettenwirksamkeit bei Zu&erkranken, die längere Zeit erfolgreich mit Su.lfonylharnstoffen behandelt worden waren, hat das Problem der sog. S e k u n d a r y e r s a g e r in zunehmendem Maße Beachtung gefunden. Die Zahlen über den Anteil der Sekundärversager bei Dauerbehandlung schwanken zwischen 14 und 30/o (56, 166, 234, 194). Uber die Ursache dieser Erscheinung besteht keine einheitliche Auffassung. Daß äußere Faktoren, wie Diätfehler, Infektionen u. ä. das Phänomen der nachlassenden Tablettenwirkung nicht erklären können, wird jedoch allgemein anerkannt. Auch dürfte die Annahme, daß es sich bei diesen Fällen um verkappte Primärversager" gehandelt haben könne, die nur durch die strenge Diät während der Einstellungsperiode in der Klinik scheinbar auf die orale Therapie ansprachen (58), nur in sehr seltenen Fällen zutreffen. Auffallen muß es dagegen, daß es sich bei der Mehrzahl dieser Kranken um solche handelt, die vor der Umstellung auf Tabletten bereits Insulin erhalten hatten (194, 241, 147). Ebenso ist es bemerkenswert, daß nicht bei denjenigen Kranken das Spätversagen auftritt, die am längsten unter der Tablettentherapie stehen, sondern der größte Teil innerhalb der ersten 6 Monate der Therapie zur Beobachtung gelangt (76, 242, 296).Von den verschiedenen Hypothesen, die zur Erklärung angeboten wurden, und die von der einfachen Feststellung einer ,,Tachyphylaxie" (149) über die Erwägung einer Antikörperbildung gegen das betreffende Sulfonylharnstoffpräparat (194) bis zur Diskussion einer Erschöpfung der Insulinproduktion in den B-Zellen der Versagerfälle reichen (147, 242), verdient besonders die letztere wegen der so gravierenden Anhaltspunkte für eine Stimulierung der endogenen Insulinsekretion und -produktion durch die Sulfonylharnstoffe Beachtung (vgl. unseren Beitrag S. 1568 dieser Zeitschrift).Eine Erschöpfung der B-Zellen müßte sich jedoch nicht nur in einer anhaltenden Stoffwechseldekompensation unter Tabletten, gleichgültig welche Dosissteigerung erfolgt oder welches Präparat verwandt wird, zu erkennen geben, sondern auch in einem absolut höheren exogenen Insulinbedarf nach Rücksetzung des unter Sulforiylharnstoffen entgleisten Patienten auf Insulin. Wie wir bei mehreren Gelegenheiten betonten (241, 242, 243), war dies bisher jedoch nicht der Fall. In Ubereinstimmung mit Heinsen (147), Mohnike (221) u. a. haben wir feststellen können, daß 1. nur bei einem sehr kleinen Teil der Sekundärversager ein höherer Insulinverbrauch festzustellen ist und 2. dieses Vorkommnis sich dann durchaus im Rahmen dessen hält, was uns über Schwankungen des Fremdinsulinbedarfs auch von der Insulinbehandlung schon seit langem vertraut ist. Wenn wir somit die Auffassung vertraten, daß Anhaltspunkte für eine irreversible Erschöpfung der B-Zellen durch die Tablettentherapie bisher fehlen, so erwogen wir doch die Möglichkeit, daß eine reversible Erschöpfung eines überforderten B-Zellenapparates das Sekundär...

Pectin, a dietary fiber, is a polysaccharide that is widely used in food industry as a gelling agent. In addition, prebiotic and beneficial immunomodulatory effects of pectin have been demonstrated, leading to increased importance as food supplement. However, as cases of anaphylactic reactions after consumption of pectin-supplemented foods have been reported, the present study aims to evaluate the allergy risk of pectin. This is of particular importance since most of the pectin used in the food industry is extracted from citrus or apple pomace. Both contain several allergens such as non-specific lipid transfer proteins (nsLTPs), known to induce severe allergic reactions, which could impair the use of pectins in nsLTP allergic patients. Therefore, the present study for the first time was performed to analyze residual nsLTP content in two commercial pectins using different detection methods. Results showed the analytical sensitivity was diminished by the pectin structure. Finally, spiking of pectin with allergenic peach nsLTP Pru p 3 led to the conclusion that the potential residual allergen content in both pectins is below the threshold to induce anaphylactic reactions in nsLTP-allergic patients. This data suggests that consumption of the investigated commercial pectin products provides no risk for inducing severe reactions in nsLTP-allergic patients.

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Peach allergy is among the most frequent food allergies in the Mediterranean area, often eliciting severe anaphylactic reactions in patients. Due to the risk of severe symptoms, studies in humans are limited, leading to a lack of therapeutic options. This study aimed to develop a peach allergy mouse model as a tool to better understand the pathomechanism and to allow preclinical investigations on the development of optimized strategies for immunotherapy. CBA/J mice were sensitized intraperitoneally with peach extract or PBS, using alum as adjuvant. Afterwards, extract was administered intragastrically to involve the intestinal tract. Allergen provocation was performed via intraperitoneal injection of extract, measuring drop of body temperature as main read out of anaphylaxis. The model induced allergy-related symptoms in mice, including decrease of body temperature. Antibody levels in serum and intestinal homogenates revealed a Th2 response with increased levels of mMCPT-1, peach- and Pru p 3-specific IgE, IgG1 and IgG2a as well as increased levels of IL-4 and IL-13. FACS analysis of small intestine lamina propria revealed increased amounts of T cells, neutrophils and DCs in peach allergic mice. These data suggest the successful establishment of a peach allergy mouse model, inducing systemic as well as local gastrointestinal reactions.

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