Human milk IgA promotes normal immune development by limiting Th17-inducing <i>Erysipelatoclostridium ramosum</i> in the infant gut
Abstract
The gut microbiota is highly dynamic during the first year of life and plays a crucial role in immune development. Breastfeeding is known to support infant health, but the contributions of the numerous breastmilk components to gut microbiota and immune maturation remain unclear. Secretory IgA (SIgA), the most abundant antibody in human milk, is a key modulator of gut microbiota composition. We have shown previously that mouse milk SIgA protects against asthma by limiting segmented filamentous bacteria in mice. The present study uncovers a similar mechanism in humans. Using human milk from the CHILD Cohort Study, we define a relationship between human milk SIgA and infant gut microbiota composition. This leads to the identification of Erysipelatoclostridium ramosum as a key player in immune development, which is controlled by milk SIgA. Cell culture modeling demonstrates that SIgA restricts the capacity of E. ramosum to adhere to the intestinal epithelium and to induce Th17 responses, which are implicated in allergic and other chronic diseases.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Katherine Donald
Department of Microbiology and Immunology, University of British Columbia
Antonio Serapio-Palacios
Department of Microbiology and Molecular Genetics, University of California
Tahereh Bozorgmehr
Michael Smith Laboratories, University of British Columbia
Mandi Ma
Department of Microbiology and Immunology, University of British Columbia
Ma Andrea Isabelle Garcia
Department of Microbiology and Immunology, University of British Columbia
Charisse Petersen
Department of Pediatrics, British Columbia Children’s Hospital, University of British Columbia
Piushkumar Mandhane
Department of Pediatrics, University of Alberta
Padmaja Subbarao
Translational Medicine Program, The Hospital for Sick Children
Theo J. Moraes
Translational Medicine Program, The Hospital for Sick Children
Elinor Simons
Section of Allergy and Immunology, Department of Pediatrics and Child Health, University of Manitoba
Stuart Turvey
Department of Microbiology and Immunology, University of British Columbia
Meghan B. Azad
Department of Immunology, University of Manitoba
B. Brett Finlay
Department of Microbiology and Immunology, University of British Columbia