Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial
Brooke C. Wilson,
Éadaoin M. Butler,
Celia P. Grigg,
José G.B. Derraik,
Valentina Chiavaroli,
Nicholas Walker,
Suma Thampi,
Christine Creagh,
Abigail J. Reynolds,
Tommi Vatanen,
Justin M. O'Sullivan,
Wayne S. Cutfield
Affiliations
Brooke C. Wilson
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Éadaoin M. Butler
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand; A Better Start – National Science Challenge, Auckland, New Zealand
Celia P. Grigg
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand
José G.B. Derraik
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand; A Better Start – National Science Challenge, Auckland, New Zealand; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Endocrinology Department, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China
Valentina Chiavaroli
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand; Neonatal Intensive Care Unit, Pescara Public Hospital, Pescara, Italy
Nicholas Walker
Department of Obstetrics and Gynaecology, Auckland City Hospital, Auckland, New Zealand.
Suma Thampi
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Christine Creagh
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Abigail J. Reynolds
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Tommi Vatanen
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand; The Broad Institute of MIT and Harvard, Cambridge, MA, USA
Justin M. O'Sullivan
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand; The Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand; Brain Research New Zealand, University of Auckland, Auckland, New Zealand; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom
Wayne S. Cutfield
Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand; A Better Start – National Science Challenge, Auckland, New Zealand; Endocrinology Department, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China; Corresponding author at: Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Background: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257). Methods: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events. Findings: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment. Interpretation: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome. Funding: Health Research Council of New Zealand, A Better Start – National Science Challenge.
