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Butyrate Enhances Desensitization Induced by Oral Immunotherapy in Cow's Milk Allergic Mice.
Vonk, Marlotte M; Blokhuis, Bart R J; Diks, Mara A P; Wagenaar, Laura; Smit, Joost J; Pieters, Raymond H H; Garssen, Johan; Knippels, Léon M J; van Esch, Betty C A M.
Afiliação
  • Vonk MM; Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, Netherlands.
  • Blokhuis BRJ; Immunology Platform, Danone Nutricia Research, Uppsalalaan 12, 3584 CT PO Box 80141, 3508 TC, Utrecht, Netherlands.
  • Diks MAP; Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, Netherlands.
  • Wagenaar L; Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, Netherlands.
  • Smit JJ; Department of Immunotoxicology, Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, Netherlands.
  • Pieters RHH; Department of Immunotoxicology, Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, Netherlands.
  • Garssen J; Department of Immunotoxicology, Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, Netherlands.
  • Knippels LMJ; Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, Netherlands.
  • van Esch BCAM; Immunology Platform, Danone Nutricia Research, Uppsalalaan 12, 3584 CT PO Box 80141, 3508 TC, Utrecht, Netherlands.
Mediators Inflamm ; 2019: 9062537, 2019.
Article em En | MEDLINE | ID: mdl-30800003
BACKGROUND: In previous studies, we showed that a fructo-oligosaccharide- (FOS-) supplemented diet enhanced oral immunotherapy (OIT) efficacy in a mouse model for cow's milk allergy. Fermentation of FOS by intestinal bacteria leads to production of short-chain fatty acids (SCFA) including butyrate. AIM: To investigate the contribution of butyrate in the enhanced efficacy of OIT + FOS. METHODS: C3H/HeOuJ mice were sensitized and received OIT with or without FOS or butyrate supplementation. After treatment, whole blood was collected to conduct a basophil activation test (BAT) and allergen challenges were performed to measure acute allergic symptoms. CD4 + CD25 + regulatory T cells (Tregs) were isolated from treated mice or differentiated in vitro and used in a bone marrow-derived mast cell (BMMC) suppression assay. Cecum content was collected to analyze SCFA concentrations. RESULTS: Allergen-induced basophil activation was reduced in OIT + butyrate samples compared to OIT. Accordingly, the acute allergic skin response and mast cell degranulation upon challenge were reduced in OIT + butyrate and OIT + FOS mice compared to sensitized controls. Butyrate was increased in the cecum content of OIT + FOS mice compared to OIT mice and sensitized controls. Treg-mediated BMMC suppression was enhanced after in vivo butyrate and FOS exposure in combination with OIT but with a more pronounced effect for butyrate. CONCLUSION: Butyrate supplementation enhanced OIT-induced desensitization of basophils and mast cells and Treg functionality. Only OIT + FOS treatment induced potential microbial alterations, shown by increased butyrate levels in cecum content. Both butyrate and FOS are promising candidates to improve OIT efficacy in human studies to treat food allergies.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Butiratos / Dessensibilização Imunológica / Hipersensibilidade Alimentar Limite: Animals Idioma: En Revista: Mediators Inflamm Assunto da revista: BIOQUIMICA / PATOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Butiratos / Dessensibilização Imunológica / Hipersensibilidade Alimentar Limite: Animals Idioma: En Revista: Mediators Inflamm Assunto da revista: BIOQUIMICA / PATOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Holanda