TY - JOUR
T1 - Akkermansia muciniphila exacerbates food allergy in fibre-deprived mice
AU - Parrish, Amy
AU - Boudaud, Marie
AU - Grant, Erica T.
AU - Willieme, Stéphanie
AU - Neumann, Mareike
AU - Wolter, Mathis
AU - Craig, Sophie Z.
AU - De Sciscio, Alessandro
AU - Cosma, Antonio
AU - Hunewald, Oliver
AU - Ollert, Markus
AU - Desai, Mahesh S.
N1 - Funding Information:
M.S.D. was supported by the Luxembourg National Research Fund (FNR) CORE grants (C15/BM/10318186 and C18/BM/12585940) and BRIDGES grant (22/17426243); A.P. was supported by an FNR AFR individual PhD fellowship (11602973); M.B. was supported by a European Commission Horizon 2020 Marie Skłodowska-Curie Actions individual fellowship (897408); E.T.G. was supported by FNR PRIDE (17/11823097) and the Fondation du Pélican de Mie et Pierre Hippert-Faber, under the aegis of the Fondation de Luxembourg; S.Z.C. was supported by FNR PRIDE (19/14254520); and M.N. was supported by the FNR AFR bilateral grant (15/11228353). We thank MEDICE Arzneimittel Pütter GmbH & Co. KG, Germany and Theralution GmbH, Germany for funding through the public–private partnership FNR BRIDGES grant (22/17426243); the National Cytometry Platform (NCP); and the Cytométrie Pitié-Salpêtrière (CyPS) for their assistance with generating cytometry data. The NCP is supported by Luxembourg’s Ministry of Higher Education and Research (MESR) funding. We also acknowledge the support of C. Jäger, X. Dong and F. Gavotto from the Luxembourg Centre for Systems Biomedicine (LCSB) Metabolomics Platform for GC–MS analyses; G. Hansson and G. Birchenough (University of Gothenburg, Sweden) for helping us set up the assay for measuring mucus penetrability. For the purpose of open access, and in fulfilment of the obligations arising from the grant agreement, the authors have applied for a Creative Commons Attribution 4.0 International (CC BY 4.0) licence to any author-accepted paper version arising from this submission.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/10
Y1 - 2023/10
N2 - Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut bacteria trigger the breakdown of oral tolerance. Here we show that depriving specific-pathogen-free mice of dietary fibre leads to a gut microbiota signature with increases in the mucin-degrading bacterium Akkermansia muciniphila. This signature is associated with intestinal barrier dysfunction, increased expression of type 1 and 2 cytokines and IgE-coated commensals in the colon, which result in an exacerbated allergic reaction to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fibre deprivation, resulted in stronger anti-commensal IgE coating and innate type-2 immune responses, which worsened symptoms of food allergy. Our study provides important insights into how gut microbes can regulate immune pathways of food allergy in a diet-dependent manner.
AB - Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut bacteria trigger the breakdown of oral tolerance. Here we show that depriving specific-pathogen-free mice of dietary fibre leads to a gut microbiota signature with increases in the mucin-degrading bacterium Akkermansia muciniphila. This signature is associated with intestinal barrier dysfunction, increased expression of type 1 and 2 cytokines and IgE-coated commensals in the colon, which result in an exacerbated allergic reaction to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fibre deprivation, resulted in stronger anti-commensal IgE coating and innate type-2 immune responses, which worsened symptoms of food allergy. Our study provides important insights into how gut microbes can regulate immune pathways of food allergy in a diet-dependent manner.
UR - http://www.scopus.com/inward/record.url?scp=85170392713&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37696941
U2 - 10.1038/s41564-023-01464-1
DO - 10.1038/s41564-023-01464-1
M3 - Article
C2 - 37696941
SN - 2058-5276
VL - 8
SP - 1863
EP - 1879
JO - Nature Microbiology
JF - Nature Microbiology
IS - 10
ER -