Kathleen Lee-Sarwar1, Sandra Dedrick2, Babak Momeni3, Rachel S Kelly4, Robert S Zeiger5, George T O'Connor6, Megan T Sandel7, Leonard B Bacharier8, Avraham Beigelman9, Nancy Laranjo4, Diane R Gold10, Jessica Lasky-Su4, Augusto A Litonjua11, Yang-Yu Liu12, Scott T Weiss13. 1. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. 2. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Department of Biology, Boston College, Chestnut Hill, Mass. 3. Department of Biology, Boston College, Chestnut Hill, Mass. 4. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. 5. Departments of Clinical Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif. 6. Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Mass. 7. Department of Pediatrics, Boston Medical Center, Boston, Mass. 8. Department of Pediatric Allergy, Immunology, and Pulmonary, Vanderbilt Children's Hospital, Vanderbilt University Medical Center, Nashville, Tenn. 9. Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, and St Louis Children's Hospital, St Louis, Mo; Kipper Institute of Allergy and Immunology, Schneider Children's Medical Center of Israel, Tel Aviv University, Tel Aviv, Israel. 10. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass. 11. Division of Pediatric Pulmonary Medicine, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, NY. 12. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. Electronic address: yyl@channing.harvard.edu. 13. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. Electronic address: restw@channing.harvard.edu.
Abstract
BACKGROUND: While the microbiome has an established role in asthma development, less is known about its contribution to morbidity in children with asthma. OBJECTIVE: In this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we analyzed the gut microbiome and metabolome of wheeze frequency in children with asthma. METHODS: Bacterial 16S ribosomal RNA microbiome and untargeted metabolomic profiling were performed on fecal samples collected from 3-year-old children with parent-reported physician-diagnosed asthma. We analyzed wheeze frequency by calculating the proportion of quarterly questionnaires administered between ages 3 and 5 years in which parents reported the child had wheezed (wheeze proportion). Taxa and metabolites associated with wheeze were analyzed by identifying log fold changes with respect to wheeze frequency and correlation/linear regression analyses, respectively. Microbe-metabolite and microbe-microbe correlation networks were compared between subjects with high and low wheeze proportion. RESULTS: Specific taxa, including the genus Veillonella and histidine pathway metabolites, were enriched in subjects with high wheeze proportion. Among wheeze-associated taxa, Veillonella and Oscillospiraceae UCG-005, which was inversely associated with wheeze, were correlated with the greatest number of fecal metabolites. Microbial networks were similar between subjects with low versus high wheeze frequency. CONCLUSION: Gut microbiome features are associated with wheeze frequency in children with asthma, suggesting an impact of the gut microbiome on morbidity in childhood asthma.
BACKGROUND: While the microbiome has an established role in asthma development, less is known about its contribution to morbidity in children with asthma. OBJECTIVE: In this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we analyzed the gut microbiome and metabolome of wheeze frequency in children with asthma. METHODS: Bacterial 16S ribosomal RNA microbiome and untargeted metabolomic profiling were performed on fecal samples collected from 3-year-old children with parent-reported physician-diagnosed asthma. We analyzed wheeze frequency by calculating the proportion of quarterly questionnaires administered between ages 3 and 5 years in which parents reported the child had wheezed (wheeze proportion). Taxa and metabolites associated with wheeze were analyzed by identifying log fold changes with respect to wheeze frequency and correlation/linear regression analyses, respectively. Microbe-metabolite and microbe-microbe correlation networks were compared between subjects with high and low wheeze proportion. RESULTS: Specific taxa, including the genus Veillonella and histidine pathway metabolites, were enriched in subjects with high wheeze proportion. Among wheeze-associated taxa, Veillonella and Oscillospiraceae UCG-005, which was inversely associated with wheeze, were correlated with the greatest number of fecal metabolites. Microbial networks were similar between subjects with low versus high wheeze frequency. CONCLUSION: Gut microbiome features are associated with wheeze frequency in children with asthma, suggesting an impact of the gut microbiome on morbidity in childhood asthma.
Authors: Richard J Martin; Stanley J Szefler; Tonya S King; Monica Kraft; Homer A Boushey; Vernon M Chinchilli; Timothy J Craig; Emily A Dimango; Aaron Deykin; John V Fahy; Elliot Israel; Stephen C Lazarus; Robert F Lemanske; Frank T Leone; Gene R Pesola; Stephen P Peters; Christine A Sorkness; Lisa A Szwejbka; Michael E Wechsler Journal: J Allergy Clin Immunol Date: 2007-01 Impact factor: 10.793
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Authors: Anne M Fitzpatrick; Daniel J Jackson; David T Mauger; Susan J Boehmer; Wanda Phipatanakul; William J Sheehan; James N Moy; Ian M Paul; Leonard B Bacharier; Michael D Cabana; Ronina Covar; Fernando Holguin; Robert F Lemanske; Fernando D Martinez; Jacqueline A Pongracic; Avraham Beigelman; Sachin N Baxi; Mindy Benson; Kathryn Blake; James F Chmiel; Cori L Daines; Michael O Daines; Jonathan M Gaffin; Deborah Ann Gentile; W Adam Gower; Elliot Israel; Harsha Vardhan Kumar; Jason E Lang; Stephen C Lazarus; John J Lima; Ngoc Ly; Jyothi Marbin; Wayne Morgan; Ross E Myers; J Tod Olin; Stephen P Peters; Hengameh H Raissy; Rachel G Robison; Kristie Ross; Christine A Sorkness; Shannon M Thyne; Stanley J Szefler Journal: J Allergy Clin Immunol Date: 2016-10-21 Impact factor: 10.793