Se Jin Song1, Jincheng Wang2, Cameron Martino3, Lingjing Jiang4, Wesley K Thompson4, Liat Shenhav5, Daniel McDonald6, Clarisse Marotz6, Paul R Harris7, Caroll D Hernandez7, Nora Henderson8, Elizabeth Ackley9, Deanna Nardella10, Charles Gillihan8, Valentina Montacuti8, William Schweizer11, Melanie Jay8, Joan Combellick12, Haipeng Sun2, Izaskun Garcia-Mantrana13, Fernando Gil Raga14, Maria Carmen Collado13, Juana I Rivera-Viñas15, Maribel Campos-Rivera16, Jean F Ruiz-Calderon17, Rob Knight18, Maria Gloria Dominguez-Bello19. 1. Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA. 2. Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901, USA. 3. Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA. 4. Division of Biostatistics, University of California, San Diego, La Jolla 92093, CA, USA. 5. Department of Computer Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. 6. Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. 7. Department of Infectious Diseases and Pediatric Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. 8. Departments of Medicine and Population Health, New York University Grossman School of Medicine, New York University, New York, NY 10016, USA. 9. Yale New Haven Hospital, New Haven, CT 06510, USA. 10. Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. 11. Department of Obstetrics and Gynecology, New York University Grossman School of Medicine, New York University, New York, NY 10016, USA. 12. Yale University School of Nursing, VA Connecticut Healthcare System, West Haven, CT 06516, USA. 13. Department of Biotechnology, Institute of Agrochemistry and Food Technology-Spanish National Research Council (IATA-CSIC), 46980 Paterna, Spain. 14. Department of Obstetrics and Gynecology, Manises Hospital, 46940 Manises, Spain. 15. Department of Obstetrics and Gynecology, Medical Science Campus, University of Puerto Rico, San Juan, PR 00925, USA. 16. Center for Community Outreach for Health Across the Lifespan, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00925, USA. 17. Medical Science Campus, University of Puerto Rico, San Juan, PR 00925, USA. 18. Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Department of Computer Science & Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla 92093, CA, USA. 19. Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901, USA; Department of Anthropology, Rutgers University, New Brunswick, NJ 08901, USA; New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ 08901, USA; Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada. Electronic address: mg.dominguez-bello@rutgers.edu.
Abstract
BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING: C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING: C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
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