title: Post-sensitization administration of non-digestible oligosaccharides andBifidobacterium breveM-16V reduces allergic symptoms in mice.
abstract: To support dietary management of severe cow's milk allergic infants, a synbiotic mixture of non-digestible oligosaccharides andBifidobacterium breveM-16V (B. breve) was designed from source materials that are completely cow's milk-free. It was investigated whether this specific synbiotic concept can reduce an established food allergic response in a research model for hen's egg allergy. Mice were orally sensitized once a week for 5 weeks to ovalbumin (OVA) using cholera toxin (CT) as an adjuvant. Non-sensitized mice received CT in PBS only. Sensitized mice were fed a control diet or a diet enriched with short-chain- (scFOS) and long-chain fructo-oligosaccharides (lcFOS),B. breveor scFOSlcFOS +B. brevefor 3 weeks starting after the last sensitization. Non-sensitized mice received the control diet. Anaphylactic shock symptoms, acute allergic skin responses and serum specific IgE, mMCP-1 and galectin-9 were measured upon OVA challenge. Activated Th2-, Th1-cells and regulatory T-cells were quantified in spleen and mesenteric lymph nodes (MLN) and cytokine profiles were analyzed. Short chain fatty acids (SCFA) were measured in ceacal samples. The acute allergic skin response was reduced in mice fed the scFOSlcFOS +B. brevediet compared to mice fed any of the other diets. A reduction in mast cell degranulation (mMCP-1) and anaphylactic shock symptoms was also observed in these mice. Unstimulated splenocyte cultures produced increased levels of IL10 and IFNg in mice fed the scFOSlcFOS +B. brevediet. Correspondingly, increased percentages of activated Th1 cells were observed in the spleen. Allergen-specific re-stimulation of splenocytes showed a decrease in IL5 production. In summary; post-sensitization administration of scFOSlcFOS +B. brevewas effective in reducing allergic symptoms after allergen challenge. These effects coincided with changes in regulatory and effector T-cell subsets and increases in the SCFA propionic acid. These results suggest immune modulatory benefits of dietary intervention with a unique combination of scFOSlcFOS +B. brevein established food allergy. Whether these effects translate to human applications is subject for ongoing clinical studies.
authors.affiliation: Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands; Nutricia ResearchUtrechtThe Netherlands.
authors.forename: Betty C A M
authors.initials: BC
authors.lastname: van Esch
authors.affiliation: Faculty of Science Divison of Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Abbring
authors.affiliation: Faculty of Science Divison of Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands.
authors.forename: Mara A P
authors.initials: MA
authors.lastname: Diks
authors.affiliation: Faculty of Science Divison of Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands.
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Dingjan
authors.affiliation: Nutricia Research Nutricia Advanced Medical Nutrition Utrecht the Netherlands.
authors.forename: Lucien F
authors.initials: LF
authors.lastname: Harthoorn
authors.affiliation: Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands; Nutricia ResearchNutricia Advanced Medical NutritionUtrechtthe Netherlands.
authors.forename: A Paul
authors.initials: AP
authors.lastname: Vos
authors.affiliation: Faculty of ScienceDivison of PharmacologyUtrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands; Nutricia ResearchUtrechtThe Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
mesh_terms: D000818:Animals; D000069984:Bifidobacterium breve; D002417:Cattle; D002645:Chickens; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007223:Infant; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000627:therapeutic use*; D010047:Ovalbumin; D058616:Synbiotics
chemical_list: D009844:Oligosaccharides; D010047:Ovalbumin
keywords: Bifidobacterium breve M‐16V; FOS; T cell subsets; Th1‐cells; acute allergic skin response; cow's milk allergy; fructo‐oligosaccharide; galectin‐9; immunoglobulins; inulin; mast cell; non‐digestible oligosaccharides; prebiotics; probiotics; propionic acid; regulatory T‐cells; short chain fatty acids; synbiotics