Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.

Charles Gillihan, Maria Gloria Dominguez-Bello, Rob Knight, Jean F Ruiz-Calderon, Maribel Campos-Rivera, Juana I Rivera-Viñas, Maria Carmen Collado, Fernando Gil Raga, Izaskun Garcia-Mantrana, Haipeng Sun, Joan Combellick, Melanie Jay, William Schweizer, Valentina Montacuti, Se Jin Song, Deanna Nardella, Elizabeth Ackley, Nora Henderson, Caroll D Hernandez, Paul R Harris, Clarisse Marotz, Daniel McDonald, Liat Shenhav, Wesley K Thompson, Lingjing Jiang, Cameron Martino, Jincheng Wang

Journal: Med (New York, N.Y.) 2022;2(8):951-964.e5

PMID: 35590169

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Plain Language Summary

Studies on model organisms show that foetal development can be modulated by microbial products from the pregnant mother’s microbiota, and early colonisation is critical for immune system development. However, natural transmission and colonisation of maternal microbes is impaired by caesarean section (CS) delivery. The aim of this study was to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. This study is a large observational study of 177 infants born to 174 mothers. Physicians assessed healthy mothers who were set to deliver vaginally or by scheduled CS. Results demonstrate that microbial differences associated with delivery mode can be reduced by exposure to a vaginal microbial source at birth. In fact, birth mode significantly differentiated infant gut and skin microbiome development, and that seeding worked to adjust the trajectory of CS-delivered infants through partial restoration of microbiome features associated with a vaginal delivery. Authors conclude that restoring natural exposures at birth may be one way to reduce the risk of CS-associated diseases such as obesity, asthma, allergies, and immune disfunctions. However, randomised clinical trials on large cohorts are needed to gain conclusive evidence for microbial restoration at birth improving health outcomes.

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.

Address: 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 Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901, USA.; 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.; Division of Biostatistics, University of California, San Diego, La Jolla 92093, CA, USA.; Department of Computer Science, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.; Department of Infectious Diseases and Pediatric Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.; Departments of Medicine and Population Health, New York University Grossman School of Medicine, New York University, New York, NY 10016, USA.; Yale New Haven Hospital, New Haven, CT 06510, USA.; Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.; Department of Obstetrics and Gynecology, New York University Grossman School of Medicine, New York University, New York, NY 10016, USA.; Yale University School of Nursing, VA Connecticut Healthcare System, West Haven, CT 06516, USA.; Department of Biotechnology, Institute of Agrochemistry and Food Technology-Spanish National Research Council (IATA-CSIC), 46980 Paterna, Spain.; Department of Obstetrics and Gynecology, Manises Hospital, 46940 Manises, Spain.; Department of Obstetrics and Gynecology, Medical Science Campus, University of Puerto Rico, San Juan, PR 00925, USA.; Center for Community Outreach for Health Across the Lifespan, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00925, USA.; Medical Science Campus, University of Puerto Rico, San Juan, PR 00925, USA.; 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.; 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: [email protected].

DOI: 10.1016/j.medj.2021.05.003

Patient Centred Factor

Mediators: Vaginal microbiota

Physical Environment

Infectious Agents

Clinical Imbalances

Gastro-intestinal

Laboratory Testing

Saliva Stool

Nutrition Evidence Keywords

Obesity Microbiome Microbiota

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MeSH Terms: Cesarean Section, Citizenship, Female, Humans, Infant, Infant, Newborn, Longitudinal Studies, Microbiota, Pregnancy, RNA, Ribosomal, 16S