This study systematically reviewed and quantified the relationship between exposure to antibiotic... more This study systematically reviewed and quantified the relationship between exposure to antibiotics during the first 2 years of life and the risk of allergies/atopies including hay fever, eczema, food allergy, positive skin prick testing (SPT), or elevated allergen-specific serum/plasma immunoglobulin (Ig) E levels later in life. PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models. Earlylife exposure to antibiotics appears to be related to an increased risk of allergic symptoms of hay fever, eczema, and food allergy later in life. The summary OR for the risk of hay fever (22 studies) was 1.23, 95% confidence interval (CI):1.13-1.34; I 2 : 77.0%. The summary OR for the risk of eczema (22 studies) was 1.26, 95% CI: 1.15-1.37; I 2 : 74.2%, and the summary OR for food allergy (3 studies) was 1.42, 95% CI: 1.08-1.87; I 2 : 80.8%. However, no association was found for antibiotics exposure early in life and objective atopy measurements including positive SPT or elevated allergen-specific serum/plasma IgE levels.
Previously, it was demonstrated that degranulation of RBL-2H3 mast cells is enhanced by α 5 β 1 i... more Previously, it was demonstrated that degranulation of RBL-2H3 mast cells is enhanced by α 5 β 1 integrin very late antigen-5 (VLA-5)-mediated adhesion to fibronectin. However, RBL-2H3 cells adhere nonspecifically to various substrates, and we therefore used mast cells cultured from mouse bone marrow (BMMC) to investigate the effect of adhesion to fibronectin on degranulation. It has been demonstrated previously that Mn 2+ induces a conformational change of VLA-5 into high-affinity for fibronectin. In our experiments, Mn 2+-induced adhesion to fibronectin enhanced allergen-induced mast cell degranulation in vitro. Surprisingly, adhesion to fibronectin induced by Mn 2+ but also by Zn 2+ , Ni 2+ , and Co 2+ , metals that are known to induce contact hypersensitivity responses, directly triggered mast cell degranulation in vitro in absence of an antigenic stimulus. This effect could be blocked by soluble arginin-glycineaspartic acid (RGD) confirming a role for VLA-5. In addition, local injection of BMMC stimulated in vitro with Mn 2+ , into the skin of BALB/c mice resulted in spontaneous activation and enhanced allergen-induced activation of these cells in vivo. This response was also attenuated with soluble RGD peptide. In conclusion, our data show that VLA-5 can modulate mast cell sensitivity for antigenic stimulation and provide a plausible explanation for hypersensitivity responses to various metals in which cation-induced integrin-mediated adhesion directly triggers degranulation.
Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the... more Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the effects of specific probiotic strains still remain unclear. Here, we assess the therapeutic effects of two probiotic strains, Lactobacillus rhamnosus NutRes 1 and Bifidobacterium breve NutRes 204 on a dextran sodium sulphate (DSS)-induced chronic murine colitis model. The chronic colitis was induced by two DSS treatment cycles with a rest period of 10 days (the remission or resolution phase). The probiotic supplementation was started during the resolution phase, after the first DSS treatment cycle, and continued until the end of the experiment. In addition to clinical observations made during the experiment, cellular infiltration was measured along with mRNA expression of pro-inflammatory cytokines, T cell-associated cytokines, and Toll like receptors (TLR) in the inflamed colon after second DSS treatment cycle. L. rhamnosus, but not B. breve, rapidly and effectively improved the DSS-in...
diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination ... more diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination of galacto-oligosaccharides and long-chain fructo-oligosaccharides with BB was less potent in this model. Conclusion These findings show that synbiotic dietary supplementation can affect respiratory allergic inflammation induced by HDM. The combination of FFBB was most effective in the prevention of HDM-induced airway inflammation in mice.
Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75-119 85 mouse model for cow's mil... more Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75-119 85 mouse model for cow's milk allergy. This effect was even more pronounced in combination with a diet containing a specific non-digestible oligosaccharide mixture of sc-Galacto-(scGOS), lc-Fructo-(lcFOS) and Acidic-(pAOS) oligosaccharides (in a 9:1:1 ratio). We hypothesized that these hydrolysates contain peptides that can induce the observed tolerance. Therefore we investigated the potential of synthetic -lactoglobulin peptides, with or without a diet containing ScGOS/lsFOS/pAOS, to induce tolerance in this mouse model.
The integrity of the epithelial layer in the gastrointestinal tract protects organisms from expos... more The integrity of the epithelial layer in the gastrointestinal tract protects organisms from exposure to luminal antigens, which are considered the primary cause of chronic intestinal inflammation and allergic responses. The common wheat-associated fungal toxin deoxynivalenol acts as a specific disruptor of the intestinal tight junction network and hence might contribute to the pathogenesis of inflammatory bowel diseases. The aim of the current study was to assess whether defined galacto-oligosaccharides (GOSs) can prevent deoxynivalenol-induced epithelial dysfunction. Human epithelial intestinal Caco-2 cells, pretreated with different concentrations of GOS (0.5%, 1%, and 2%) for 24 h, were stimulated with 4.2-μM deoxynivalenol (24 h), and 6/7-wk-old male B6C3F1 mice were fed a diet supplemented with 1% GOS for 2 wk before being orally exposed to deoxynivalenol (25 mg/kg body weight, 6 h). Barrier integrity was determined by measuring transepithelial electrical resistance (TEER) and ...
Product development in the health and life sciences is experiencing a shift from the development ... more Product development in the health and life sciences is experiencing a shift from the development of specific-target pharmaceutical products to multi-target nutritional therapy products such as medical nutrition. Medical nutrition consists of targeted nutritional compositions for intervention in disease progression and symptom alleviation. The European medical nutrition market is a fast-growing market at an early stage of industry development. Future growth of this market depends on the capability of the industry to innovate. In this study we applied the "barriers to innovation approach", meaning that innovative action in a market is decreased due to specific innovation barriers. The European medical nutrition market is currently experiencing an innovation-gap due to these wide-ranging barriers. To stimulate innovation within a market, one must first know which specific barriers to overcome. The aim of this study was therefore to identify the main barriers that are experienced by KOLs in the innovation process of medical nutrition. Qualitative semi-structured interviews were conducted with 17 key opinion leaders in the field of medical nutrition (medical doctors, dieticians and researchers). Root cause analysis is applied to the interview transcripts to identify the main barriers of innovation in this market with its underlying causes. The barriers and causes are visualized in a causal tree showing the interrelations of the causes of the innovation barriers. 21 barriers were identified and grouped into four main barrier categories: financial, clinical trials, collaboration and knowledge. Principal causes according to the key opinion leaders are: the lack of awareness among healthcare personnel, government and insurance companies concerning medical nutrition; the differences in objectives between industry and academia; and the difficulty to carry out randomized controlled trials. The majority of innovation barriers in this industry have proven to be exogenous. To eradicate these barriers and stimulate innovation, industry, academia and politics all must closely collaborate.
Previously, it was shown that depletion and stabilization of the mucosal mast cell around the tim... more Previously, it was shown that depletion and stabilization of the mucosal mast cell around the time of challenge were very effective in reducing delayed-type hypersensitivity (DTH) reactions in the small intestine of the rat. The role of mucosal mast cells in the early component of intestinal DTH reaction was further investigated in this study. In vivo small intestinal vascular leakage and serum levels of rat mast cell protease II (RMCP II) were determined within 1 h after intragastric challenge of rats that had been sensitized with dinitrobenzene 5 days before. A separate group of rats was used to study vasopermeability in isolated vascularly perfused small intestine after in vitro challenge. To investigate the effects of mast cell stabilization on the early events of the DTH reaction, doxantrazole was used. The influence of sensory nerves was studied by means of neonatal capsaicin-induced depletion of sensory neuropetides. Within 1 h after challenge, a significant increase in vascu...
This study systematically reviewed and quantified the relationship between exposure to antibiotic... more This study systematically reviewed and quantified the relationship between exposure to antibiotics during the first 2 years of life and the risk of allergies/atopies including hay fever, eczema, food allergy, positive skin prick testing (SPT), or elevated allergen-specific serum/plasma immunoglobulin (Ig) E levels later in life. PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models. Earlylife exposure to antibiotics appears to be related to an increased risk of allergic symptoms of hay fever, eczema, and food allergy later in life. The summary OR for the risk of hay fever (22 studies) was 1.23, 95% confidence interval (CI):1.13-1.34; I 2 : 77.0%. The summary OR for the risk of eczema (22 studies) was 1.26, 95% CI: 1.15-1.37; I 2 : 74.2%, and the summary OR for food allergy (3 studies) was 1.42, 95% CI: 1.08-1.87; I 2 : 80.8%. However, no association was found for antibiotics exposure early in life and objective atopy measurements including positive SPT or elevated allergen-specific serum/plasma IgE levels.
Previously, it was demonstrated that degranulation of RBL-2H3 mast cells is enhanced by α 5 β 1 i... more Previously, it was demonstrated that degranulation of RBL-2H3 mast cells is enhanced by α 5 β 1 integrin very late antigen-5 (VLA-5)-mediated adhesion to fibronectin. However, RBL-2H3 cells adhere nonspecifically to various substrates, and we therefore used mast cells cultured from mouse bone marrow (BMMC) to investigate the effect of adhesion to fibronectin on degranulation. It has been demonstrated previously that Mn 2+ induces a conformational change of VLA-5 into high-affinity for fibronectin. In our experiments, Mn 2+-induced adhesion to fibronectin enhanced allergen-induced mast cell degranulation in vitro. Surprisingly, adhesion to fibronectin induced by Mn 2+ but also by Zn 2+ , Ni 2+ , and Co 2+ , metals that are known to induce contact hypersensitivity responses, directly triggered mast cell degranulation in vitro in absence of an antigenic stimulus. This effect could be blocked by soluble arginin-glycineaspartic acid (RGD) confirming a role for VLA-5. In addition, local injection of BMMC stimulated in vitro with Mn 2+ , into the skin of BALB/c mice resulted in spontaneous activation and enhanced allergen-induced activation of these cells in vivo. This response was also attenuated with soluble RGD peptide. In conclusion, our data show that VLA-5 can modulate mast cell sensitivity for antigenic stimulation and provide a plausible explanation for hypersensitivity responses to various metals in which cation-induced integrin-mediated adhesion directly triggers degranulation.
Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the... more Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the effects of specific probiotic strains still remain unclear. Here, we assess the therapeutic effects of two probiotic strains, Lactobacillus rhamnosus NutRes 1 and Bifidobacterium breve NutRes 204 on a dextran sodium sulphate (DSS)-induced chronic murine colitis model. The chronic colitis was induced by two DSS treatment cycles with a rest period of 10 days (the remission or resolution phase). The probiotic supplementation was started during the resolution phase, after the first DSS treatment cycle, and continued until the end of the experiment. In addition to clinical observations made during the experiment, cellular infiltration was measured along with mRNA expression of pro-inflammatory cytokines, T cell-associated cytokines, and Toll like receptors (TLR) in the inflamed colon after second DSS treatment cycle. L. rhamnosus, but not B. breve, rapidly and effectively improved the DSS-in...
diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination ... more diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination of galacto-oligosaccharides and long-chain fructo-oligosaccharides with BB was less potent in this model. Conclusion These findings show that synbiotic dietary supplementation can affect respiratory allergic inflammation induced by HDM. The combination of FFBB was most effective in the prevention of HDM-induced airway inflammation in mice.
Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75-119 85 mouse model for cow's mil... more Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75-119 85 mouse model for cow's milk allergy. This effect was even more pronounced in combination with a diet containing a specific non-digestible oligosaccharide mixture of sc-Galacto-(scGOS), lc-Fructo-(lcFOS) and Acidic-(pAOS) oligosaccharides (in a 9:1:1 ratio). We hypothesized that these hydrolysates contain peptides that can induce the observed tolerance. Therefore we investigated the potential of synthetic -lactoglobulin peptides, with or without a diet containing ScGOS/lsFOS/pAOS, to induce tolerance in this mouse model.
The integrity of the epithelial layer in the gastrointestinal tract protects organisms from expos... more The integrity of the epithelial layer in the gastrointestinal tract protects organisms from exposure to luminal antigens, which are considered the primary cause of chronic intestinal inflammation and allergic responses. The common wheat-associated fungal toxin deoxynivalenol acts as a specific disruptor of the intestinal tight junction network and hence might contribute to the pathogenesis of inflammatory bowel diseases. The aim of the current study was to assess whether defined galacto-oligosaccharides (GOSs) can prevent deoxynivalenol-induced epithelial dysfunction. Human epithelial intestinal Caco-2 cells, pretreated with different concentrations of GOS (0.5%, 1%, and 2%) for 24 h, were stimulated with 4.2-μM deoxynivalenol (24 h), and 6/7-wk-old male B6C3F1 mice were fed a diet supplemented with 1% GOS for 2 wk before being orally exposed to deoxynivalenol (25 mg/kg body weight, 6 h). Barrier integrity was determined by measuring transepithelial electrical resistance (TEER) and ...
Product development in the health and life sciences is experiencing a shift from the development ... more Product development in the health and life sciences is experiencing a shift from the development of specific-target pharmaceutical products to multi-target nutritional therapy products such as medical nutrition. Medical nutrition consists of targeted nutritional compositions for intervention in disease progression and symptom alleviation. The European medical nutrition market is a fast-growing market at an early stage of industry development. Future growth of this market depends on the capability of the industry to innovate. In this study we applied the "barriers to innovation approach", meaning that innovative action in a market is decreased due to specific innovation barriers. The European medical nutrition market is currently experiencing an innovation-gap due to these wide-ranging barriers. To stimulate innovation within a market, one must first know which specific barriers to overcome. The aim of this study was therefore to identify the main barriers that are experienced by KOLs in the innovation process of medical nutrition. Qualitative semi-structured interviews were conducted with 17 key opinion leaders in the field of medical nutrition (medical doctors, dieticians and researchers). Root cause analysis is applied to the interview transcripts to identify the main barriers of innovation in this market with its underlying causes. The barriers and causes are visualized in a causal tree showing the interrelations of the causes of the innovation barriers. 21 barriers were identified and grouped into four main barrier categories: financial, clinical trials, collaboration and knowledge. Principal causes according to the key opinion leaders are: the lack of awareness among healthcare personnel, government and insurance companies concerning medical nutrition; the differences in objectives between industry and academia; and the difficulty to carry out randomized controlled trials. The majority of innovation barriers in this industry have proven to be exogenous. To eradicate these barriers and stimulate innovation, industry, academia and politics all must closely collaborate.
Previously, it was shown that depletion and stabilization of the mucosal mast cell around the tim... more Previously, it was shown that depletion and stabilization of the mucosal mast cell around the time of challenge were very effective in reducing delayed-type hypersensitivity (DTH) reactions in the small intestine of the rat. The role of mucosal mast cells in the early component of intestinal DTH reaction was further investigated in this study. In vivo small intestinal vascular leakage and serum levels of rat mast cell protease II (RMCP II) were determined within 1 h after intragastric challenge of rats that had been sensitized with dinitrobenzene 5 days before. A separate group of rats was used to study vasopermeability in isolated vascularly perfused small intestine after in vitro challenge. To investigate the effects of mast cell stabilization on the early events of the DTH reaction, doxantrazole was used. The influence of sensory nerves was studied by means of neonatal capsaicin-induced depletion of sensory neuropetides. Within 1 h after challenge, a significant increase in vascu...
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