Secretory IgA in breast milk protects against asthma through modulation of the gut microbiota
Katherine Donald,
Antonio Serapio-Palacios,
Zachary Gerbec,
Tahereh Bozorgmehr,
Ravi Holani,
Ana Raquel Cruz,
Pamela Schnupf,
B. Brett Finlay
Affiliations
Katherine Donald
Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Antonio Serapio-Palacios
Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Zachary Gerbec
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada
Tahereh Bozorgmehr
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Ravi Holani
Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Ana Raquel Cruz
Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Laboratory of Host-Microbiota Interaction, 75015 Paris, France
Pamela Schnupf
Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, Laboratory of Host-Microbiota Interaction, 75015 Paris, France
B. Brett Finlay
Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Corresponding author
Summary: Asthma susceptibility is linked to dysbiosis in early-life gut microbiota, and the antibody secretory immunoglobulin (Ig)A (SIgA) is a key determinant of gut microbiota composition. SIgA is obtained through breast milk during the critical early-life window. We use a mouse model of SIgA deficiency and the house dust mite (HDM) model of asthma to elucidate the role of maternal SIgA in modulating the early-life gut microbiota and asthma protection. Mice that do not receive maternal SIgA display a transient bloom of segmented filamentous bacteria (SFB) in the small intestine during the early post-weaning period. Mice that do not receive maternal SIgA also display elevated T helper type 17 (Th17) cell activation in the intestine, which persists into adulthood and is associated with more severe inflammation in response to the HDM model of asthma. This study demonstrates a mechanism by which breast-milk-derived SIgA influences immune development and asthma susceptibility by modulating the early-life gut microbiota.
