Does exposing cesarean-delivered newborns to the vaginal microbiome restore microbiome development? More clinical trials are needed before conclusions can be made

Although the World Health Organization states that caesarian section is medically necessary in 10%-15% of pregnancies, this mode of delivery is on the rise globally, with some countries such as Brazil, the Dominican Republic, Iran and China achieving a rate of more than 60% of deliveries. This is worrying as cesarean deliveries mean newborns do not receive their first exposure to the microbiota through the vaginal canal, which could mean an increase in disease risk later in life.

Indeed, the differences in microbiome development in caesarean-born infants compared to vaginally born infants may persist up to 4 years of age, with lasting health consequences that include a higher risk of overweight and obesity that, at least in mice, has been shown to be independent of antibiotic intake.

In the light of these findings, scientists have recently been interested in figuring out whether transferring the mother’s vaginal microbiome to the newborn is causally associated with health outcomes.

A small pilot study in 2016 showed that swabbing cesarean-born babies immediately after birth with the mother’s vaginal secretions (also known as ‘vaginal seeding’) can partially restore their microbiome and most notably the oral and skin microbiomes.

Two new studies provide contradictory findings on the effect of vaginal seeding on microbiome trajectory during early life.

An observational study in 177 babies from USA, Spain, Chile and Bolivia over the first year of life showed that swabbing 30 babies born by cesarean section after birth with a maternal vaginal gauze stored in the vagina for 1 hour before the cesarean section procedure partly normalized not only gut microbiota development, but also oral and skin microbiota development.

The microbiota of the cesarean section-seeded babies was close to that of vaginally born babies, especially in fecal samples. Changes in microbiome variability across body sites in cesarean section-seeded infants, somewhere in the middle between vaginal and cesarean section-born infants, showed that vaginal seeding contributed to stabilizing microbiome development.

The authors also identified specific bacterial taxa associated with effective seeding that varied depending on the body site. For instance, Bacteroides, Streptococcus and Clostridium genera were found to be enriched in cesarean section-seeded infants over the study period.

No complications were detected in seeded infants during the follow-up period of the study.

The second study consisted of a pilot randomized controlled trial that evaluated, during the first 3 months of life, the efficacy of vaginal seeding by oral administration at birth to restore gut microbiome development in 12 infants from New Zealand born by cesarean section. The oral administration of maternal vaginal microbiota did not alter gut microbiome composition or functions in cesarean section-born infants either at 1 month or 3 months of age.

In addition, despite the viability of vaginal microbes in the seeding inoculum, maternal vaginal engraftment was almost absent. The authors hypothesized that maternal fecal, rather than vaginal, microbiota could provide a more effective method for restoring the depleted levels of Bacteroides species in cesarean section-born infants. This is in line with findings presented by Moran Yassour during the last Gut Microbiota for Health World Summit held in Madrid.

The authors also tracked adverse events. They found no serious adverse events associated with vaginal seeding and neither did they detect any changes in anthropometric measures and body composition in response to vaginal seeding.

Although limited in sample size and duration compared to the first observational study, the second study is a randomized clinical trial that provides stronger evidence.

On the whole, the findings suggest that acquiring maternal vaginal microbes may not always normalize microbiome development in babies. Despite potential health benefits, it should be acknowledged that vaginal seeding also has potential risks, such as infections (e.g. group B Streptococcus). A limitation of the presented studies is that we have no sense yet of whether this procedure affects actual health outcomes. As this perspective in the British Journal of Obstetrics and Gynaecology claims: “more randomised trials of vaginal seeding in caesarean-delivered newborns are needed to clarify to what extent this procedure changes infant microbiome development and whether changes in the microbiome alter the risk of caesarean section-associated diseases.”

References:

Fouhy F, Watkins C, Hill CJ, et al. Perinatal factors affect the gut microbiota up to four years after birth. Nat Commun. 2019; 10(1):1517. doi: 10.1038/s41467-019-09252-4.

Martinez KA, Devlin JC, Lacher CR, et al. Increased weight gain by C-section: Functional significance of the primordial microbiome. Sci Adv. 3(10):eaao1874. doi: 10.1126/sciadv.aao1874.

Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016; 22(3):250-253. doi: 10.1038/nm.4039.

Song SJ, Wang J, Martino C, et al. Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding. Med. 2021. doi: 10.1016/j.medj.2021.05.003.

Wilson BC, Butler EM, Grigg CP, et al. 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. EBioMedicine. 2021; 69:103443. doi: 10.1016/j.ebiom.2021.103443.

Mueller NT, Dominguez-Bello MG, Appel LJ, et al. ‘Vaginal seeding’ after a caesarean section provides benefits to newborn children: FOR: Does exposing caesarean-delivere newborns to the vaginal microbiome affect their chronic disease risk? The critical need for trials of ‘vaginal seeding’ during caesare. BJOG. 2020; 127(2):301. doi: 10.1111/1471-0528.15979.