Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans.

BACKGROUND: Prebiotic galacto- and fructo-oligosaccharides (scGOS/lcFOS) resembling non-digestible oligosaccharides in human milk reduce the development of atopic disorders. However, the underlying mechanisms are still unclear. Galectins are soluble-type lectins recognizing ß-galactoside containing glycans. Galectin-9 has been shown to regulate mast cell degranulation and T-cell differentiation. In this study, the involvement of galectin-9 as a mechanism by which scGOS/lcFOS in combination with Bifidobacterium breve M-16V protects against acute allergic symptoms was investigated. METHODS: Mice were sensitized orally to whey, while being fed with a diet containing scGOS/lcFOS and Bifidobacterium breve M-16V (GF/Bb) or a control diet. Galectin-9 expression was determined by immunohistochemistry in the intestine and measured in the serum by ELISA. T-cell differentiation was investigated in the mesenteric lymph nodes (MLN) as well as in galectin-9-exposed peripheral blood mononuclear cells (PBMC) cultures. Sera of the mice were evaluated for the capacity to suppress mast cell degranulation using a RBL-2H3 degranulation assay. In addition, in a double-blind, placebo-controlled multicenter trial, galectin-9 levels were measured in the sera of 90 infants with atopic dermatitis who received hydrolyzed formulae with or without GF/Bb. RESULTS: Galectin-9 expression by intestinal epithelial cells and serum galectin-9 levels were increased in mice and humans following dietary intervention with GF/Bb and correlated with reduced acute allergic skin reaction and mast cell degranulation. In addition, GF/Bb enhanced T(h)1- and T(reg)-cell differentiation in MLN and in PBMC cultures exposed to galectin-9. CONCLUSIONS: Dietary supplementation with GF/Bb enhances serum galectin-9 levels, which associates with the prevention of allergic symptoms.

No detectable beneficial systemic immunomodulatory effects of a specific synbiotic mixture in infants with atopic dermatitis.

BACKGROUND: In a murine model of allergic inflammation, Bifidobacterium breve M-16V has been shown to reduce IL-4 and IgE by inducing IL-10 and IFN-γ. However, it remains unknown whether this strain has the same effect in humans with allergic disease. OBJECTIVE: To determine the effects of Bifidobacterium breve M-16V combined with a prebiotic oligosaccharide mixture (synbiotic) on atopic markers, ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) and circulating regulatory T cell percentage in infants with atopic dermatitis. METHODS: In a double-blind, placebo-controlled multi-centre trial, 90 infants with atopic dermatitis, age <7 months, were randomized to receive an infant formula with Bifidobacterium breve M-16V and a mixture of short chain galactooligosaccharides and long chain fructooligosaccharides (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. At week 0 and 12, plasma levels of IL-5, IgG1, IgG4, CTACK and TARC, ex vivo cytokine responses by PBMCs and percentage of regulatory T cells, were determined. RESULTS: There were no significant differences between the synbiotic and the placebo group in IL-5, IgG1, IgG4, CTACK and TARC levels and ex vivo cytokine production by anti-CD3/anti-CD28-stimulated PBMCs. With allergen-specific stimuli, we found a decreased IL-12p40/70 and IL-12p70 production in response to egg allergen (P = 0.04 and P = 0.01, respectively) and decreased IL-12p70 production in response to peanut allergen (P = 0.003) in the synbiotic compared with the placebo group. Circulating regulatory T cell percentage did not significantly differ between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: This synbiotic mixture has no detectable effect on plasma levels of the analysed atopic disease markers, ex vivo cytokine production and circulating regulatory T cell percentage in infants with atopic dermatitis, besides down-regulation of IL-12 production in egg- and peanut-stimulated PBMCs. These results do not support the use of this synbiotic in clinical practice.

Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis.

BACKGROUND: Infants with atopic dermatitis (AD) have a high risk of developing asthma. We investigated the effect of early intervention with synbiotics, a combination of probiotics and prebiotics, on the prevalence of asthma-like symptoms in infants with AD. METHODS: In a double-blind, placebo-controlled multicentre trial, ninety infants with AD, age <7\ months, were randomized to receive an extensively hydrolyzed formula with Bifidobacterium breve M-16V and a galacto/fructooligosaccharide mixture (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. After 1 year, the prevalence of respiratory symptoms and asthma medication use was evaluated, using a validated questionnaire. Also, total serum IgE and specific IgE against aeroallergens were determined. FINDINGS: Seventy-five children (70.7% male, mean age 17.3 months) completed the 1-year follow-up evaluation. The prevalence of 'frequent wheezing' and 'wheezing and/or noisy breathing apart from colds' was significantly lower in the synbiotic than in the placebo group (13.9%vs 34.2%, absolute risk reduction (ARR) -20.3%, 95% CI -39.2% to -1.5%, and 2.8%vs 30.8%, ARR -28.0%, 95% CI -43.3% to -12.5%, respectively). Significantly less children in the synbiotic than in the placebo group had started to use asthma medication after baseline (5.6%vs 25.6%, ARR -20.1%, 95% CI -35.7% to -4.5%). Total IgE levels did not differ between the two groups. No children in the synbiotic and five children (15.2%) in the placebo group developed elevated IgE levels against cat (ARR -15.2%, 95% CI -27.4% to -2.9%). CONCLUSION: These results suggest that this synbiotic mixture prevents asthma-like symptoms in infants with AD.

Effect of a new synbiotic mixture on atopic dermatitis in infants: a randomized-controlled trial.

BACKGROUND: Clinical trials investigating the therapeutic effect of probiotics on atopic dermatitis (AD) show inconsistent results. Better results can possibly be achieved by combining probiotics with prebiotics, i.e. synbiotics. OBJECTIVE: To investigate the therapeutic effect of a synbiotic mixture on the severity of AD in infants. METHODS: In a double-blind, placebo-controlled multi-centre trial, 90 infants with AD [SCORing Atopic Dermatitis (SCORAD) score > or =15], aged < 7 months and exclusively formula fed, were randomly assigned to receive either an extensively hydrolysed formula with Bifidobacterium breve M-16V and a galacto-/fructooligosaccharide mixture (Immunofortis), or the same formula without synbiotics for 12 weeks. The primary outcome was severity of AD, assessed using the SCORAD index. A secondary outcome measure was intestinal microbiota composition. RESULTS: There was no difference in SCORAD score improvement between the synbiotic and the placebo group. The synbiotic group did have a significantly higher percentage of bifidobacteria (54.7% vs. 30.1%, P<0.001) and significantly lower percentages of Clostridium lituseburense/Clostridium histolyticum (0.5 vs. 1.8, P=0.02) and Eubacterium rectale/Clostridium coccoides (7.5 vs. 38.1, P<0.001) after intervention than the placebo group. In the subgroup of infants with IgE-associated AD (n=48), SCORAD score improvement was significantly greater in the synbiotic than in the placebo group at week 12 (-18.1 vs. -13.5 points, P=0.04). CONCLUSIONS: This synbiotic mixture does not have a beneficial effect on AD severity in infants, although it does successfully modulate their intestinal microbiota. Further randomized-controlled trials should explore a possible beneficial effect in IgE-associated AD.

Infant feeding and allergy prevention: a review of current knowledge and recommendations. A EuroPrevall state of the art paper.

The relationship between infant feeding patterns and the later development of food allergies has been the focus of much debate and research over the last decade. National recommendations have been made by many countries on how to feed infants to reduce the risk of food allergy but due to the lack of firm evidence the recommendations differ widely. This review has been developed as part of EuroPrevall, a European multicentre research project funded by the European Union, to document the differing feeding recommendations made across Europe, to investigate the current evidence base for any allergy prevention feeding recommendations and to identify areas where further research is needed. This review will also provide information which, when combined with the infant feeding data collected as part of EuroPrevall, will give an indication of compliance to national feeding guidelines which can be utilised to assess the effectiveness of current dissemination and implementation strategies.

[Wegener's granulomatosis in 2 adolescents]. / De ziekte van Wegener bij 2 adolescenten.

Wegener's granulomatosis was diagnosed in 2 boys, aged 17 and 16 years. The first presented with pain in the right flank, without coughing or dyspnoea. He did have peaks of fever, night sweats, weight loss, headache, and epistaxis. The second presented with progressive dyspnoea, haemoptysis, malaise, and headache. Because an infection was suspected, both were given antibiotics, but without effect. Chest X-rays revealed infiltrative abnormalities. A lung biopsy in the first patient and a nasal biopsy in the second revealed a granulomatous inflammation, and both patients had an elevated titre of antineutrophilic cytoplasmic antibodies (ANCA), with a cytoplasmic pattern, and an elevated result of the ELISA test for antiproteinase-3 (PR3). Both patients recovered after aggressive immunosuppressive treatment. Wegener's granulomatosis is a systemic necrotising vasculitis, mostly localised in airways and kidneys. The disease is very rare in children, but may be life-threatening. Therefore, in children with pulmonary problems resistant to antibiotics, it is important to consider a diagnosis of Wegener's granulomatosis and test for ANCA and PR3.

High incidence of acute lung injury in children with Down syndrome.

OBJECTIVE: Acute respiratory tract infection is a common reason for hospitalization in children with Down syndrome (CDS) and is characterized by a high morbidity. The severe course of disease in CDS may be related to a higher incidence of acute lung injury (ALI). This study evaluated the incidence of ALI and acute respiratory distress syndrome (ARDS) in mechanically ventilated CDS. DESIGN AND SETTING: Retrospective cohort study in a pediatric ICU. PATIENTS AND PARTICIPANTS: Cases were all mechanically ventilated CDS admitted to our unit between January 1998 and July 2005. All mechanically ventilated patients without Down syndrome from January 1998 to January 2001 served as controls. Postoperative patients (cases and controls) and those with a cardiac left to right shunt were excluded. MEASUREMENTS AND RESULTS: The main outcome measure was the incidence of ALI and ARDS. The criteria for ALI were met in 14 of 24 CDS (58.3%) in 41 of 317 of controls (12.9%; OR 9.4, 95% CI 3.9-22.6). The criteria for ARDS were met in 11 of 24 CDS (46%) and in 21 of 317 of controls (7%; OR 11.9, 95% CI 4.8-29.8). None of the CDS with ALI died; in the control group ten patients with ALI died. CONCLUSIONS: CDS had a significantly higher incidence of ALI and ARDS than children without Down syndrome. The explanation for this remains to be elucidated; further study is necessary before clinical implications become clear.