Anne G Hoen1, Jing Li2, Lisa A Moulton3, George A O'Toole4, Molly L Housman4, Devin C Koestler5, Margaret F Guill3, Jason H Moore2, Patricia L Hibberd6, Hilary G Morrison7, Mitchell L Sogin7, Margaret R Karagas8, Juliette C Madan9. 1. Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH. 2. Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH. 3. Division of Allergy and Pediatric Pulmonology, Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH. 4. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH. 5. Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS. 6. Division of Global Health, Department of Pediatrics, Massachusetts General Hospital, Boston, MA. 7. Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA. 8. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH. 9. Division of Neonatology, Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH. Electronic address: Juliette.C.Madan@Dartmouth.Edu.
Abstract
OBJECTIVE: To examine patterns of microbial colonization of the respiratory and intestinal tracts in early life in infants with cystic fibrosis (CF) and their associations with breastfeeding and clinical outcomes. STUDY DESIGN: A comprehensive, prospective longitudinal analysis of the upper respiratory and intestinal microbiota in a cohort of infants and young children with CF followed from birth was performed. Genus-level microbial community composition was characterized using 16S-targeted pyrosequencing, and relationships with exposures and outcomes were assessed using linear mixed-effects models, time-to-event analysis, and principal components analysis. RESULTS: Sequencing of 120 samples from 13 subjects collected from birth to 34 months revealed relationships between breastfeeding, microbial diversity in the respiratory and intestinal tracts, and the timing of onset of respiratory complications, including exacerbations and colonization with Pseudomonas aeruginosa. Fluctuations in the abundance of specific bacterial taxa preceded clinical outcomes, including a significant decrease in bacteria of the genus Parabacteroides within the intestinal tract prior to the onset of chronic P aeruginosa colonization. Specific assemblages of bacteria in intestinal samples, but not respiratory samples, were associated with CF exacerbation in early life, indicating that the intestinal microbiome may play a role in lung health. CONCLUSIONS: Our findings relating breastfeeding to respiratory outcomes, gut diversity to prolonged periods of health, and specific bacterial communities in the gut prior to respiratory complications in CF highlight a connection between the intestinal microbiome and health and point to potential opportunities for antibiotic or probiotic interventions. Further studies in larger cohorts validating these findings are needed.
OBJECTIVE: To examine patterns of microbial colonization of the respiratory and intestinal tracts in early life in infants with cystic fibrosis (CF) and their associations with breastfeeding and clinical outcomes. STUDY DESIGN: A comprehensive, prospective longitudinal analysis of the upper respiratory and intestinal microbiota in a cohort of infants and young children with CF followed from birth was performed. Genus-level microbial community composition was characterized using 16S-targeted pyrosequencing, and relationships with exposures and outcomes were assessed using linear mixed-effects models, time-to-event analysis, and principal components analysis. RESULTS: Sequencing of 120 samples from 13 subjects collected from birth to 34 months revealed relationships between breastfeeding, microbial diversity in the respiratory and intestinal tracts, and the timing of onset of respiratory complications, including exacerbations and colonization with Pseudomonas aeruginosa. Fluctuations in the abundance of specific bacterial taxa preceded clinical outcomes, including a significant decrease in bacteria of the genus Parabacteroides within the intestinal tract prior to the onset of chronic P aeruginosa colonization. Specific assemblages of bacteria in intestinal samples, but not respiratory samples, were associated with CF exacerbation in early life, indicating that the intestinal microbiome may play a role in lung health. CONCLUSIONS: Our findings relating breastfeeding to respiratory outcomes, gut diversity to prolonged periods of health, and specific bacterial communities in the gut prior to respiratory complications in CF highlight a connection between the intestinal microbiome and health and point to potential opportunities for antibiotic or probiotic interventions. Further studies in larger cohorts validating these findings are needed.
Authors: John Penders; Carel Thijs; Cornelis Vink; Foekje F Stelma; Bianca Snijders; Ischa Kummeling; Piet A van den Brandt; Ellen E Stobberingh Journal: Pediatrics Date: 2006-08 Impact factor: 7.124
Authors: Maria G Dominguez-Bello; Elizabeth K Costello; Monica Contreras; Magda Magris; Glida Hidalgo; Noah Fierer; Rob Knight Journal: Proc Natl Acad Sci U S A Date: 2010-06-21 Impact factor: 11.205
Authors: A Tanaka; M Seki; S Yamahira; H Noguchi; K Kosai; M Toba; Y Morinaga; T Miyazaki; K Izumikawa; H Kakeya; Y Yamamoto; K Yanagihara; T Tashiro; N Kohda; S Kohno Journal: Lett Appl Microbiol Date: 2011-05-31 Impact factor: 2.858
Authors: Angela Polizzi; Ruggiero Francavilla; Giuseppe Castaldo; Teresa Santostasi; Rossella Tomaiuolo; Antonio Manca; Francesco De Robertis; Luigi Mappa; Francesca Paola Oliverio; Francesco Salvatore; Nicola Rigillo Journal: Am J Med Genet A Date: 2005-02-01 Impact factor: 2.802
Authors: Scott D Sagel; Ronald L Gibson; Julia Emerson; Sharon McNamara; Jane L Burns; Jeffrey S Wagener; Bonnie W Ramsey Journal: J Pediatr Date: 2008-09-25 Impact factor: 4.406
Authors: Michael J Cox; Martin Allgaier; Byron Taylor; Marshall S Baek; Yvonne J Huang; Rebecca A Daly; Ulas Karaoz; Gary L Andersen; Ronald Brown; Kei E Fujimura; Brian Wu; Diem Tran; Jonathan Koff; Mary Ellen Kleinhenz; Dennis Nielson; Eoin L Brodie; Susan V Lynch Journal: PLoS One Date: 2010-06-23 Impact factor: 3.240
Authors: François Meurens; Mustapha Berri; Richard H Siggers; Benjamin P Willing; Henri Salmon; Andrew G Van Kessel; Volker Gerdts Journal: PLoS One Date: 2007-07-25 Impact factor: 3.240
Authors: Katherine M Antosca; Diana A Chernikova; Courtney E Price; Kathryn L Ruoff; Kewei Li; Margaret F Guill; Natalie R Sontag; Hilary G Morrison; Shuyu Hao; Mitchell L Drumm; Todd A MacKenzie; Dana B Dorman; Lynn M Feenan; Molly A Williams; John Dessaint; Irene H Yuan; Brian J Aldrich; Lisa A Moulton; Lily Ting; Ana Martinez-Del Campo; Edward J Stewart; Margaret R Karagas; George A O'Toole; Juliette C Madan Journal: J Bacteriol Date: 2019-07-24 Impact factor: 3.490
Authors: Brett R Loman; Chandra L Shrestha; Rohan Thompson; Judith A Groner; Asuncion Mejias; Kathryn L Ruoff; George A O'Toole; Michael T Bailey; Benjamin T Kopp Journal: Pediatr Pulmonol Date: 2020-04-10
Authors: Mansi Kanhere; Jiabei He; Benoit Chassaing; Thomas R Ziegler; Jessica A Alvarez; Elizabeth A Ivie; Li Hao; John Hanfelt; Andrew T Gewirtz; Vin Tangpricha Journal: J Clin Endocrinol Metab Date: 2018-02-01 Impact factor: 5.958
Authors: Claire Healy; Natalia Munoz-Wolf; Janné Strydom; Lynne Faherty; Niamh C Williams; Sarah Kenny; Seamas C Donnelly; Suzanne M Cloonan Journal: Respir Res Date: 2021-04-29