The gut microbiota of people with asthma influences lung inflammation in gnotobiotic mice
Naomi G. Wilson,
Ariel Hernandez-Leyva,
Anne L. Rosen,
Natalia Jaeger,
Ryan T. McDonough,
Jesus Santiago-Borges,
Michael A. Lint,
Thomas R. Rosen,
Christopher P. Tomera,
Leonard B. Bacharier,
S. Joshua Swamidass,
Andrew L. Kau
Affiliations
Naomi G. Wilson
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Ariel Hernandez-Leyva
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Anne L. Rosen
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Natalia Jaeger
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Ryan T. McDonough
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Jesus Santiago-Borges
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Michael A. Lint
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Thomas R. Rosen
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Christopher P. Tomera
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
Leonard B. Bacharier
Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Monroe Carell Jr Children’s Hospital at Vanderbilt University Medical Center, Nashville, TN 37232, USA
S. Joshua Swamidass
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Andrew L. Kau
Division of Allergy and Immunology, Department of Medicine and Center for Women’s Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Summary: The gut microbiota in early childhood is linked to asthma risk, but may continue to affect older patients with asthma. Here, we profile the gut microbiota of 38 children (19 asthma, median age 8) and 57 adults (17 asthma, median age 28) by 16S rRNA sequencing and find individuals with asthma harbored compositional differences from healthy controls in both adults and children. We develop a model to aid the design of mechanistic experiments in gnotobiotic mice and show enterotoxigenic Bacteroides fragilis (ETBF) is more prevalent in the gut microbiota of patients with asthma compared to healthy controls. In mice, ETBF, modulated by community context, can increase oxidative stress in the lungs during allergic airway inflammation (AAI). Our results provide evidence that ETBF affects the phenotype of airway inflammation in a subset of patients with asthma which suggests that therapies targeting the gut microbiota may be helpful tools for asthma control.
