Development of gut mycobiome in infants and young children: a prospective cohort study

Abstract

Background: The composition of the gut fungal microbiome, mycobiome, is likely associated with human health. Yet, the development of gut mycobiome is poorly understood in infants and children. Here we investigate how perinatal events influence the development of gut mycobiome.

Methods: In this prospective cohort study of 140 infants, we used ITS gene sequencing of fecal samples from birth to the age of 18 months. We compared gut mycobiome composition according to delivery mode and exposure to intrapartum antibiotics during vaginal delivery.

Results: At birth, gut mycobiome were dominated by the genus Candida, at 6-month stool samples by Malassezia and Cystofilobasidium, and the 18-month stool samples by Trichosporon and unidentified fungi. Perinatal factors altered mycobiome. At 18 months, gut mycobiome of infants born vaginally consisted mostly of Trichosporon (32%) and unidentified fungi (31%), while those born via Cesarean section delivery samples had mycobiome dominated by Saccharomyces (50%). At the age of 18 months, those exposed to intrapartum antibiotics had mycobiome dominated by Trichosporon (66%) not seen in those unexposed to antibiotics.

Conclusions: Delivery mode and exposure to intrapartum antibiotic prophylaxis were markedly associated with gut mycobiome composition from birth to 18 months of age.

Impact: The composition of the gut mycobiome is likely associated with human health. Yet, the development of gut mycobiome is poorly understood in infants and children. In this prospective cohort study, delivery mode and exposure to intrapartum antibiotic prophylaxis were markedly associated with gut mycobiome composition from birth to 18 months of age. The impact of intrapartum antibiotic prophylaxis on fungal microbiome in vaginally born infants, previously shown to influence gut bacteriome composition, may be explained by the interaction between bacteria and fungi. Gut mycobiome composition likely deserves further investigation in relation to gut microbiome and health in children.

Fig. 1. Taxonomic figures, alpha diversity, and beta diversity of all the stool samples by age at sampling.

a All the phyla present in the samples for each time point. b The 20 most common genera in the samples for each time point. The rest of the genera are collapsed in the “other” group. c Shannon Index, using Kruskal–Wallis H as the statistical test. d Observed features, using Kruskal–Wallis H as the statistical test. e Bray–Curtis Dissimilarity between samples based on the sample age group. PERMANOVA was used as the statistical test for beta diversity.

Fig. 2. Taxonomic figures for each sample type based on the mode of delivery.

a Relative abundances of the taxa at the phylum level. b The top 20 most abundant genera with the rest collapsed into the “other” group. c Changes in the abundance of Ascomycota (top) and Basidiomycota (bottom) over time in the vaginal delivery and Cesarean delivery groups. d Changes in the abundance of Candida (top left), Malassezia (top right), Saccharomyces (bottom left) and Trichosporon (bottom right) over time in the vaginal delivery and Cesarean delivery groups.

Fig. 3. Alpha and beta diversity of all the samples by the mode of delivery.

a Meconium, b 6-month stool, c 18-month stool. Alpha diversity metrics used: Shannon Index, observed features, with the Kruskal–Wallis H used as a statistical test. Beta diversity metric used: Bray–Curtis Dissimilarity, with PERMANOVA used as a statistical test. p values are shown in the respective figures.

Fig. 4. Taxonomic figures for each time point showing the effect of intrapartum antibiotic exposure in vaginal delivery samples.

a Relative abundances of the taxa at the phylum level. b The top 20 most abundant genera with the rest collapsed into the “other” group. c Changes in the abundance of Ascomycota (top) and Basidiomycota (bottom) over time in the groups with and without intrapartum antibiotics. d Changes in the abundance of Candida (top left), Malassezia (top right), Saccharomyces (bottom left), and Trichosporon (bottom right) over time in the groups with and without intrapartum antibiotic exposure.

Fig. 5. Alpha and beta diversity of vaginal delivery samples showing the effect of the intrapartum antibiotic exposure.

a Meconium samples. b 6-month stool samples. c 18-month stool samples. Alpha diversity metrics used: Shannon Index, observed features, with Kruskal–Wallis H used as a statistical test. Beta diversity metric used: Bray–Curtis Dissimilarity, with PERMANOVA used as a statistical test. p values are shown in the respective figures.