Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy.

Autor:	Han K; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China., Xie F; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Animasahun O; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Nenwani M; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Kitamoto S; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Kim Y; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Phoo MT; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA., Xu J; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Wuchu F; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Omoloja K; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Achreja A; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Choppara S; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Li Z; Graduate Program in Biostatistics, University of Washington, Seattle, WA, USA., Gong W; Departments of Head and Neck Surgery and of Cancer Biology, the University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Cho YS; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Dobson H; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Ahn J; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, Dongguk University, Seoul, Republic of Korea., Zhou X; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Huang X; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., An X; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA., Kim A; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA., Xu Y; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Wu Q; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA., Lee SH; Department of Biomedical Engineering, Dongguk University, Seoul, Republic of Korea., O'Konek JJ; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI, USA., Xie Y; Department of Computational Mathematics, Science and Engineering, Michigan State University, East Lansing, MI, USA.; Department of Statistics and Probability, Michigan State University, East Lansang, MI, USA., Lei YL; Departments of Head and Neck Surgery and of Cancer Biology, the University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Kamada N; Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.; WPI Immunology Frontier Research Center, Osaka University, Suita, Japan., Nagrath D; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA., Moon JJ; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. moonjj@umich.edu.; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. moonjj@umich.edu.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. moonjj@umich.edu.; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. moonjj@umich.edu.
Jazyk:	angličtina
Zdroj:	Nature materials [Nat Mater] 2024 Oct; Vol. 23 (10), pp. 1444-1455. Date of Electronic Publication: 2024 Jul 08.
DOI:	10.1038/s41563-024-01909-w
Abstrakt:	Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ + and interleukin-10 + regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases. (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze:	MEDLINE
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