TY - JOUR
T1 - The gut microbiota of people with asthma influences lung inflammation in gnotobiotic mice
AU - Wilson, Naomi G.
AU - Hernandez-Leyva, Ariel
AU - Rosen, Anne L.
AU - Jaeger, Natalia
AU - McDonough, Ryan T.
AU - Santiago-Borges, Jesus
AU - Lint, Michael A.
AU - Rosen, Thomas R.
AU - Tomera, Christopher P.
AU - Bacharier, Leonard B.
AU - Swamidass, S. Joshua
AU - Kau, Andrew L.
N1 - Funding Information:
We would like to thank our clinical study coordinators Tarisa Mantia, Caitlin O’Shaughnessy, and Shannon Rook; the physicians of Washington University Pediatric and Adolescent Ambulatory Research Consortium, especially Dr. Jane Garbutt; the Volunteer for Health registry; and the MARS participants and their families. We would also like to acknowledge Dr. Devesha Kulkarni, for her technical expertise as well as the Center for Genome Sciences Sequencing Core and Genome Technology Access Center at the McDonnell Genome Institute for sequencing services. The authors also thank Drs. Brain Laidlaw and Leyao Wang for critical reading of the manuscript and Drs Philip Ahern, Neelendu Dey, and Ansel Hsiao for thoughtful feedback on our work. A.L.K. is funded by the AAAAI Foundation Faculty Development Award and the NIH K08 AI113184 . A.H-L received funding through the NIH T32 GM007200 and F30 DK127584 . J.S-B received funding through the NIH T32 GM007067 .
Funding Information:
We would like to thank our clinical study coordinators Tarisa Mantia, Caitlin O'Shaughnessy, and Shannon Rook; the physicians of Washington University Pediatric and Adolescent Ambulatory Research Consortium, especially Dr. Jane Garbutt; the Volunteer for Health registry; and the MARS participants and their families. We would also like to acknowledge Dr. Devesha Kulkarni, for her technical expertise as well as the Center for Genome Sciences Sequencing Core and Genome Technology Access Center at the McDonnell Genome Institute for sequencing services. The authors also thank Drs. Brain Laidlaw and Leyao Wang for critical reading of the manuscript and Drs Philip Ahern, Neelendu Dey, and Ansel Hsiao for thoughtful feedback on our work. A.L.K. is funded by the AAAAI Foundation Faculty Development Award and the NIH K08 AI113184. A.H-L received funding through the NIH T32 GM007200 and F30 DK127584. J.S-B received funding through the NIH T32 GM007067. N.G.W. A.H.-L. and A.L.K. conceptualized the work. L.B.B. and A.L.K. planned the clinical study. N.G.W. A.H.-L. A.L.R. N.J. R.T.M. J.S.-B. M.A.L. C.P.T. and A.L.K. contributed to the design and conduct of experiments. N.G.W. A.H.-L. A.L.R. N.J. R.T.M. and A.L.K. analyzed the data. N.G.W. A.H.-L. T.R.R. and S.J.S. developed gnominator. N.G.W. A.H.-L. and A.L.K. drafted the manuscript. All authors interpreted the data and contributed to revising the manuscript. The authors have no competing interests to declare. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location. One or more of the authors of this paper self-identifies as a gender minority in their field of research. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. We support inclusive, diverse, and equitable conduct of research.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/2/17
Y1 - 2023/2/17
N2 - 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.
AB - 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.
KW - Immunity
KW - Medical microbiology
UR - http://www.scopus.com/inward/record.url?scp=85147414195&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.105991
DO - 10.1016/j.isci.2023.105991
M3 - Article
C2 - 36824270
AN - SCOPUS:85147414195
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 2
M1 - 105991
ER -