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.

Early life: gut microbiota and immune development in infancy.

The immune system of infants is actively downregulated during pregnancy and therefore the first months of life represent a period of heightened susceptibility to infection. After birth, there is an age-dependent maturation of the immune system. Exposure to environmental microbial components is suggested to play an important role in the maturation process. The gastrointestinal tract is the major site of interaction between the host immune system and microorganisms, both commensal as well as potentially pathogenic. It is well established that the mammalian immune system is designed to help protect the host from invading microorganisms and other danger signals. However, recent research is emerging in the field of host-microbe interactions showing that commensal microorganisms (microbiota) are most likely one of the drivers of immune development and, in turn the immune system shapes the composition of the microbiota. Specific early microbial exposure of the gut is thought to dramatically reduce the incidence of inflammatory, autoimmune and atopic diseases further fuelling the scientific view that microbial colonisation plays an important role in regulating and fine-tuning the immune system throughout life. Therefore, the use of pre-, pro- and synbiotics may result in a beneficial microbiota composition that might have a pivotal role on the prevention of several important diseases that develop in early life such as necrotizing enterocolitis and atopic eczema.

Human mesenchymal stem cells derived from bone marrow display a better chondrogenic differentiation compared with other sources.

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into several mesodermal lineages. These cells have been isolated from various tissues, such as adult bone marrow, placenta, and fetal tissues. The comparative potential of these cells originating from different tissues to differentiate into the chondrogenic lineage is still not fully defined. The aim of our study was to investigate the chondrogenic potential of MSCs isolated from different sources. MSCs from fetal and adult tissues were phenotypically characterized and examined for their differentiation capacity, based on morphological criteria and expression of extracellular matrix components. Our results show that both fetal and adult MSCs have chondrogenic potential under appropriate conditions. The capacity of bone marrow-derived MSCs to differentiate into chondrocytes was reduced on passaging of cells. MSCs of bone marrow origin, either fetal or adult, exhibit a better chondrogenesis than fetal lung- and placenta-derived MSCs, as demonstrated by the appearance of typical morphological features of cartilage, the intensity of toluidine blue staining, and the expression of collagen type II, IX, and X after culture under chondrogenic conditions. As MSCs represent an attractive tool for cartilage tissue repair strategies, our data suggest that bone marrow should be considered the preferred MSC source for these therapeutic approaches.

Specific inhibition of the classical complement pathway by C1q-binding peptides.

Undesired activation of the complement system is a major pathogenic factor contributing to various immune complex diseases and conditions such as hyperacute xenograft rejection. We aim for prevention of complement-mediated damage by specific inhibition of the classical complement pathway, thus not affecting the antimicrobial functions of the complement system via the alternative pathway and the lectin pathway. Therefore, 42 peptides previously selected from phage-displayed peptide libraries on basis of C1q binding were synthesized and examined for their ability to inhibit the function of C1q. From seven peptides that showed inhibition of C1q hemolytic activity but no inhibition of the alternative complement pathway, one peptide (2J) was selected and further studied. Peptide 2J inhibited the hemolytic activity of C1q from human, chimpanzee, rhesus monkey, rat, and mouse origin, all with a similar dose-response relationship (IC(50) 2-6 microM). Binding of C1q to peptide 2J involved the globular head domain of C1q. In line with this interaction, peptide 2J dose-dependently inhibited the binding of C1q to IgG and blocked activation of C4 and C3 and formation of C5b-9 induced via classical pathway activation, as assessed by ELISA. Furthermore, the peptide strongly inhibited the deposition of C4 and C3 on pig cells following their exposure to human xenoreactive Abs and complement. We conclude that peptide 2J is a promising reagent for the development of a therapeutic inhibitor of the earliest step of the classical complement pathway, i.e., the binding of C1q to its target.