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

Abstract

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 (CSseeded, 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.

From Short- to Long-Term Effects of C-Section Delivery on Microbiome Establishment and Host Health

“…The exposure of CSD babies to the mothers' vaginal fluids after birth allowed a partial restoration of the microbiota, which was more similar to the microbiota of VD babies than CSD with no treatment [56]. In contrast, a novel approach to vaginal seeding, consisting of orally feeding the baby vagina-extracted bacteria, did not show any differences between treated and control groups, with very little engraftment of maternal strains, suggesting that other sites, apart from the mother's vagina, could be key locations of bacterial sources during delivery [57]. Nevertheless, in mice, the co-housing of CSD and VD pups partially reverted some behavioral deficits associated with CSD [53].…”

First encounters of the microbial kind: perinatal factors direct infant gut microbiome establishment

“…For instance, the skin and vagina are thought to be the source of the gut microbiota in emergency CS, whereas the skin is considered to be the predominant microbial origin of the gut microbiota in infants born by elective CS [83] . Recent studies have attempted to utilise orally delivered fecal microbiota transplantation (FMT) and oral administration of maternal vaginal microbiota to restore disturbed intestinal microbial colonisation in CS born infants [84,85] . Despite its recent inception, FMT has yielded encouraging results [84] , while vaginal transplantation has delivered less comprehensive findings [85] .…”

“…Recent studies have attempted to utilise orally delivered fecal microbiota transplantation (FMT) and oral administration of maternal vaginal microbiota to restore disturbed intestinal microbial colonisation in CS born infants [84,85] . Despite its recent inception, FMT has yielded encouraging results [84] , while vaginal transplantation has delivered less comprehensive findings [85] .…”

Infection prevention for extremely low birth weight infants in the NICU

“…Postnatal acquisition of the microbiome plays a critical role in immune development and response. 7 , 8 The preterm infant’s microbiome is largely driven by environmental exposures in the NICU. 9 Thus, repeated courses of antibiotics, the NICU ecological environment and choice of diet (formula or breast milk) are key regulators of the microbiome and may be important in the pathogenesis of late onset sepsis (LOS) 10 , 11 , 12 In the setting of preterm rupture of membranes, the sterile or partially sterile uterine environment is compromised by exposure to genital microbes.…”

“…The mode of delivery greatly influences the kind of bacteria that colonize the newborn. 13 Caesarean-delivered infants bypass the vaginal canal secretions, which are rich in Lactobacillus, Bacteroides and Bifidobacterium species, 8 and have a microbiota composition that is different from those infants born vaginally. 14 , 15 Several studies have investigated the practice of ‘vaginal seeding,’ through swabbing the mouths and skin of caesarean-born infants in an attempt to mimic the microbiota exposure during a vaginal birth.…”