Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone.

Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db/db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.

Dietary wheat amylase trypsin inhibitors exacerbate murine allergic airway inflammation.

BACKGROUND: Wheat amylase trypsin inhibitors (ATI) are dietary non-gluten proteins that activate the toll-like receptor 4 on myeloid cells, promoting intestinal inflammation. AIM OF THE STUDY: We investigated the effects of dietary ATI on experimental allergic airway inflammation. METHODS: Mice on a gluten and ATI-free diet (GAFD), sensitized with PBS or ovalbumin (OVA) and challenged with OVA, were compared to mice on a commercial standard chow, a gluten diet naturally containing ~ 0.75% of protein as ATI (G+AD), a gluten diet containing ~ 0.19% of protein as ATI (G-AD) and a GAFD with 1% of protein as ATI (AD). Airway hyperreactivity (AHR), inflammation in bronchoalveolar lavage (BAL) and pulmonary tissue sections were analyzed. Allergic sensitization was assessed ex vivo via proliferation of OVA-stimulated splenocytes. RESULTS: Mice on a GAFD sensitized with PBS did not develop AHR after local provocation with methacholine. Mice on a GAFD or on a G-AD and sensitized with OVA developed milder AHR compared to mice fed a G+AD or an AD. The increased AHR was paralleled by increased BAL eosinophils, IL-5 and IL-13 production, and an enhanced ex vivo splenocyte activation in the ATI-fed groups. CONCLUSIONS: Dietary ATI enhance allergic airway inflammation in OVA-challenged mice, while an ATI-free or ATI-reduced diet has a protective effect on AHR. Nutritional wheat ATI, activators of intestinal myeloid cells, may be clinically relevant adjuvants to allergic airway inflammation.

Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

BACKGROUND: Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). OBJECTIVE: We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. METHODS: The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. RESULTS: Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. CONCLUSION: Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the balance of Th1/Th2 immunity and then attenuates allergic inflammatory responses significantly, as well as optimizes the structure of intestinal microbiota, which suggests potential for novel preventive and therapeutic intervention.

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Chemical mediators and the resolution of airway inflammation.

Asthma pathobiology is remarkable for chronic airway inflammation that fails to spontaneously resolve. No curative therapy is currently available. A growing body of evidence indicates that, in health, inflammation resolution is an active process orchestrated by specific chemical mediators that are elaborated to restore tissue homeostasis. Activated cell membranes release polyunsaturated fatty acids from phospholipids for enzymatic conversion to biologically active mediators with profound regulatory effects on innate and adaptive immunity. Some of these mediators carry anti-inflammatory and pro-resolving actions that are transduced in a cell-type specific manner via specific recognition sites that initiate regulatory intracellular signals, such as presqualene diphosphate remodeling, to limit pro-phlogistic cell activation. Some of these counter-regulatory lipid mediators have been identified in the airway during asthma and defects in their production are associated with disease severity. In this review, we describe the biosynthesis and bioactions of pro-resolving chemical mediators and provide examples of select mediators and their structural analogs with particular relevance to asthma.

Reduction of allergic airway eosinophilia by dietary raffinose in Brown Norway rats.

Oral administration of raffinose, a naturally occurring indigestible oligosaccharide, has reportedly ameliorated atopic dermatitis in human subjects although the mechanism is unknown. The present study investigated the effect of dietary raffinose on allergen-induced airway eosinophilia in ovalbumin-sensitised Brown Norway rats as an atopic disease model. Brown Norway rats were immunised by subcutaneous injection with ovalbumin on day 0 and fed either a control diet or the diet supplemented with raffinose (50 g/kg diet). The rats were exposed to aerosolised ovalbumin on day 20, and broncho-alveolar lavage fluid was obtained on the next day. The number of eosinophils in the fluid was significantly lower in the rats fed the raffinose diet than in those fed the control diet. Dietary raffinose significantly reduced IL-4 and IL-5 mRNA levels in lung tissue and tended to lower ovalbumin-specific Ig E levels. Suppression of eosinophilia by dietary raffinose was still observed in caecectomised and neomycin-administered rats, suggesting little contribution by the colonic bacteria to the effect of raffinose. Intraperitoneal administration of raffinose also suppressed eosinophilia. Significant concentrations of raffinose were detected in portal venous and abdominal arterial plasma after the intragastric administration of raffinose. Overall, the findings suggest that dietary raffinose ameliorates allergic airway eosinophilia at least partly via post-absorptive mechanisms in Brown Norway rats.

Treatment of delayed food allergy based on specific immunoglobulin G RAST testing.

This preliminary, descriptive study after extensive clinical experience demonstrates specific IgG food RASTs done in 114 consecutive patients with strong positive histories for delayed food allergy. Elimination of the positive foods was the sole means of treatment. The symptoms leading to the test are detailed, and the method of workup is reviewed. The overall results demonstrated a 71% success rate for all symptoms achieving at least a 75% improvement level. Of particular interest was the group of patients with chronic, disabling symptoms, unresponsive to other intensive treatments. Whereas 70% obtained 75% or more improvement, 20% of these patients obtained 100% relief.

[The histamine-free diet]. / Die histaminfreie Diät.

Food intolerance is not IgE-mediated but caused by histamine. A diminished histamine degradation based on a deficiency of diaminoxidase is suspected to be the reason. The therapeutic efficacy of a histamine-free diet was evaluated in 100 patients with food intolerance and allergic diseases, who were required to avoid fish, cheese, hardcured sausage, pickled cabbage, wine and beer for 4 weeks. Considerable improvement was observed in 57 patients, 15 of whom had total remission. The most striking treatment results were obtained in food or wine intolerance (80% P < 0.05; treatment of choice), bronchial asthma (80%), headache (64%) and urticaria (58%). After ingestion of food rich in histamine clearcut recurrence of atopic eczema was seen in 50% of the patients affected. Histamine plays a major part in food and wine intolerance. Histamine in food causes worsening of symptoms in atopics and patients suffering from headache. The results obtained indicate a deficiency of diaminoxidase in patients with intolerance to food or wine. Histamine levels in alcoholic beverages should be displayed on the labels.

[Behavior of bronchial reactivity in 50 children before and after exclusion of food allergens]. / Comportamento della reattività bronchiale in 50 ragazzi prima e dopo esclusione degli allergeni alimentari.

In this study the author has purposed to demonstrated that the food allergens increase the bronchoreactivity. This studied group was formed by 50 boys with chronic rhinitis and/or nasal perennial and/or laryngeal and bronchial obstruction, unresponsive to aeroallergens but responsive to food allergens determined with FBST test. This test is performed by making the patient go on an anallergic diet (formed by tapioca's flour, rabbit, olive oil, beets, lettuce, pear, sugar, salt for seven days). The first week are controlled the spirometric values and every week is introduced a new food with ambulatory control of spirometric values and of Raw and control of domiciliary PEF. The "trapped" reaction is "retard" with fall of all spirometric values at food allergens introduction. Then 15 boys undergone test of free running for six minutes, 15 the aspecific metacholine test and 10 both proofs. Then the 40 boys executed the food allergens exclusion from diet for a three months period; a control group of 10 boys executed the free running and the metacholine ABS and then the diagnosis of food allergens but kept a free diet. After three months the boys repeated the proofs. The group of 40 boys who executed the food allergens exclusion showed and heavy diminution of bronchoreactivity either with free running test either with metacholine ABS test.