From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "
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Abstract 1 Scope A major downside of oral immunotherapy (OIT) for food allergy is the risk of severe side effects. Non‐digestible short‐ and long‐chain fructo‐oligosaccharides (scFOS/lcFOS) reduce allergy development in murine models. Therefore, it is hypothesized that scFOS/lcFOS can also support the efficacy of OIT in a peanut allergy model. 2 Methods and Results After sensitization to peanut extract (PE) using cholera toxin, C3H/HeOuJ mice are fed a 1% scFOS/lcFOS or control diet and receive OIT (1.5 or 15 mg PE). Hereafter, mice are exposed to PE via different routes to determine the safety and efficacy of treatment in clinical outcomes, PE‐specific antibody production, and numbers of various immune cells. scFOS/lcFOS increases short‐chain fatty acid levels in the caecum and reduce the acute allergic skin response and drop in body temperature after PE exposure. Interestingly, 15 mg and 1.5 mg OIT with scFOS/lcFOS induce protection against anaphylaxis, whereas 1.5 mg OIT alone does not. OIT, with or without scFOS/lcFOS, induces PE‐specific immunoglobulin (Ig) IgG and IgA levels and increases CD103+ dendritic cells in the mesenteric lymph nodes. 3 Conclusions scFOS/lcFOS and scFOS/lcFOS combined with low dose OIT are able to protect against a peanut‐allergic anaphylactic response.
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The “as eaten” method to measure the Total Dietary Fibre content and an in vitro fermentation with colon bacteria were successfully coupled to see if fibre fractions have a prebiotic effect. Similar growth pattern for modified starch, FOS and GOS were observed (Fig A). The qPCR results indicate a significant stimulation of the growth of gut bacteria by FOS and GOS and in lesser extent by the modified starch (Fig.C). Future experiments will compare the qPCR data with metagenomic analysis of in vitro and in vivo experiments.
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In the last decade, the concept on interactions between humans, animals and their environment has drastically changed, endorsed by the One Health approach that recognizes that health of humans and animals are inextricably linked. Consideration of welfare of livestock has increased accordingly and with it, attention into the possibilities to improve livestock health via natural, more balanced nutrition is expanding. Central to effects of healthy nutrition is an optimal gastrointestinal condition which entails a well-balanced functional local immune system leading to a resilient state of well-being. This project proposal, GITools, aims to establish a toolbox of in vitro assays to screen new feed ingredients for beneficial effects on gastrointestinal health and animal well-being. GITools will focus on pig and chicken as important livestock species present in high quantities and living in close proximity to humans. GITools builds on intestinal models (intestinal cell lines and stem cell-derived organoids), biomarker analysis, and in vitro enzymatic and microbial digestion models of feed constituents. The concept of GITools originated from various individual contacts and projects with industry partners that produce animal feed (additives) or veterinary medicines. Within these companies, an urgent need exists for straightforward, well-characterized and standardized in vitro methods that provide results translatable to the in vivo situation. This to replace testing of new feed concepts in live animal. We will examine in vitro methods for their applicability with feed ingredients selected based on the availability of data from (previous) in vivo studies. These model compounds will include long and short chain fatty acids, oligosaccharides and herbal-derived components. GITools will deliver insights on the role of intestinal processes (e.g. dietary hormone production, growth of epithelial cells, barrier function and innate immune responses) in health and well-being of livestock animals and improve the efficiency of testing new feed products.
This project has received funding from the Bio-based Industries Joint Undertaking under the European Union's Horizon 2020 research and innovation programme under grant agreement No 720726LIBBIO is a European research project on Andes Lupin (Lupinus mutabilis, tarwi) cropping in marginal lands for enhanced bio economy. Lupin has the ability to fix nitrogen, mobilise soil phosphate and has low nutritional requirements for cultivation. Varieties will be chosen that give high yield of green silage or high yield of seeds which contain more than 20% oil, more than 40% protein and the remaining materials are carbohydrates, mainly oligosaccharides characterized as “prebiotics”. Andes lupin will be grown as a summer crop in N-central Europe and as winter crop in Mediterranean conditions. Pre-industrial processing is developed and optimized for the lupin, properties of the different fractions analysed, their advantage for different industrial use evaluated, and a few products developed as an example. Social and environmental impact will be evaluated as well as techno-economic viability and effect on farm and biorefinery income.This project has received funding from the Bio-based Industries Joint Undertaking under the European Union's Horizon 2020 research and innovation programme under grant agreement No 720726