Extremely preterm neonates have more Lactobacillus in meconium than very preterm neonates - the in utero microbial colonization hypothesis

Juliana Morais, Cláudia Marques, Diana Teixeira, Catarina Durão, Ana Faria, Sara Brito, Manuela Cardoso, Israel Macedo, Esmeralda Pereira, Teresa Tomé, Conceição Calhau, Juliana Morais, Cláudia Marques, Diana Teixeira, Catarina Durão, Ana Faria, Sara Brito, Manuela Cardoso, Israel Macedo, Esmeralda Pereira, Teresa Tomé, Conceição Calhau

Abstract

Growing evidence suggests that maternal microbiota can influence the neonates' gut colonization. However, the mechanisms of vertical bacterial transmission remain poorly defined. We believed that the first colonizers of the newborn come from the mother's gut and vagina during pregnancy and that this is independent of the mode of delivery. We conducted an observational longitudinal study to evaluate the link between the maternal gut microbiota and the meconium's microbiota in extremely and very preterm neonates. Bacterial DNA was extracted from samples and specific bacterial groups were quantified by RT-PCR. In this cohort of 117 preterm neonates, we detected bacterial DNA in 88% of meconium samples. Meconium microbiota of neonates born after 28 gestational weeks (very preterm neonates) showed stronger correlations with their mothers' fecal microbiota. However, neonates born before 28 gestational weeks (extremely preterm neonates) had more Lactobacillus - genus that dominated the vaginal microbiota - than very preterm neonates, regardless of the mode of delivery. Collectively, these data support the hypothesis that maternal bacteria from the gut and vagina can play a role in shaping neonates' gut microbiota and that mother-to-infant bacterial transmission is a controlled and time-specific process. ClinicalTrials.gov Identifier: NCT03663556.

Keywords: Lactobacillus; maternal microbiota; meconium; preterm neonates.

Figures

Figure 1.
Figure 1.
Sample characterization. (a) Clinical characterization of preterm neonates. (b) Specific bacterial group levels in neonates’ meconium (a, b, c), and in their mothers fecal samples (d, f, e). Negative controls for sample collection, DNA extraction and RT-PCR (n = 5). Data are expressed as mean ± SEM.
Figure 1.
Figure 1.
Sample characterization. (a) Clinical characterization of preterm neonates. (b) Specific bacterial group levels in neonates’ meconium (a, b, c), and in their mothers fecal samples (d, f, e). Negative controls for sample collection, DNA extraction and RT-PCR (n = 5). Data are expressed as mean ± SEM.
Figure 2.
Figure 2.
Scatterplots showing the association between mothers’ microbiota and their neonates’ microbiota (Spearman's correlation): (a) represent correlation between very preterm neonates and their mothers; (b) correlations of mother-infants pairs delivered by C-section.
Figure 3.
Figure 3.
(a) Content of Lactobacillus in preterm neonates’ meconium regarding gestational age and mode of deliver. (b) Content of total bacteria in preterm neonates’ meconium regarding gestational age and mode of delivery. Data are expressed as mean ± SEM.
Figure 4.
Figure 4.
Controlled and time-specific mother-to-infant bacterial transmission: (a), the vertical bacterial transmission starts mainly with Lactobacillus (predominantly from vaginal microbiota) via the vaginal ascending route; (b), during the third trimester, maternal gut bacteria is predominantly transmitted to the fetus intestine via the hematogenous route and through deglutination of amniotic fluid.
Figure 4.
Figure 4.
Controlled and time-specific mother-to-infant bacterial transmission: (a), the vertical bacterial transmission starts mainly with Lactobacillus (predominantly from vaginal microbiota) via the vaginal ascending route; (b), during the third trimester, maternal gut bacteria is predominantly transmitted to the fetus intestine via the hematogenous route and through deglutination of amniotic fluid.

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